CASE REPORT
Metastasis from squamous carcinoma of the cervix stage 1B to a borderline cystadenoma of the ovary ROARBRUUNRASMUSSEN’, BIRGITTEBRUUNRASMUSSEN‘ AND JENSB. KNUDSEN’
From the ‘Department of Gynecology & Obstetrics and t h e ‘Department of Pathology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
Acta Obstst Gynecol Scand 1992; 71: 69-71 A case of metastasis from squamous carcinoma stage 1B of the cervix to a borderline cystadenoma of the ovary is described. In addition, the patient had atypical endometrial
hyperplasia. The patient underwent a radical hysterectomy with no adjuvant postoperative treatment and has resumed work, with no sign of recurrence one year postoperatively. The aspects of the metastasis to the ovary, multiple tumors in the genital tract and tumor-to-tumor metastasis are discussed. Reports on ovarian metastasis in low-stage squamous carcinoma of the cervix are few and it still seems justified to spare the ovaries at surgery in the young patient. Key words: carcinoma of the cervix; squamous carcinoma; ovarian metastasis Submitted Januury 10, 1991 Accepted August 29, 1991
Metastasis to the ovary in cases of squamous carcinoma of the cervix is rare (1,2). There is a general consensus to avoid removing the ovaries at surgery for low-stage squamous cervical carcinoma in young females in order to preserve the endocrine function and avoid menopausal symptoms (1,2). Synchronous neoplasms of the ovary and uterus are an uncommon but well known entity with a reported incidence of less than 1% of all forms of cancer in the upper genital tract (3,4). Metastasis from one neoplasm to another tumor, whether malignant, premalignant or benign, is a rare event, but has been reported in a number of cases (5). We report a case of squamous carcinoma of the cervix with metastasis to a borderline cystadenoma of the ovary in a patient who in addition had atypical endometrial hyperplasia.
Case report A 54-year-old previously healthy female, was referred with vaginal bleeding of 3 months’ duration. She had never received hormonal treatment and had no family history of malignant disease. A t examination, a tumor protruding from the orifice of an enlarged cervix was found. The uterus was enlarged but mobile and the adnexa were unremarkable. The patient underwent cervical biopsy and curettage of the uterus, which revealed invasive squamous carcinoma of the cervix and growth of squamous carcinoma in the endometrium and endocervix. The tumor was classified as stage 1B. The patient underwent a radical hysterectomy, bilateral salpingo-oophorectomy, pelvic lymphadenectomy and appendectomy. At the time of operation the right ovary appeared to have small cysts and the left ovary appeared atrophic. The uterus was enlarged but there was no sign of tumor penetration. The patient received no postoperative adjuvant Acru Ohstrt Gynrrol Stand 71 (IYY2)
70
R. B. Rusmussen et ul.
Discussion
Fig. I . Ovary with serous cystadenoma. borderline typc of the cervix (crrrowhud). I harr = 20pm. (crrrow) and metastatic squamous carcinoma
treatment. Two months postoperatively she was referred twice to the regional hospital presenting with mild symptoms of ileus which was managed conservatively. Since then she has been well and is now, one year after surgery, free from signs of recurrence and has resumed work.
Pathologic findings The utcrus was found to be enlarged due t o a 9 X 7 cm tumor involving thc cervix and isthmus and which had spread to the uterine corpus posteriorly. There were no macroscopic signs o f tumor spread to the surface o f the uterus. The specimen included a right-side ovary measuring 3.5 x 2 x 1 cm, with several cysts. Microscopically the tumor consisted of an invasive keratinizing squamous carcinoma. It had involved thc isthmus and was spreading to the endometrium, hut had not yet penetrated the serosal surface. There was spread to the myometrium and in one section a tumor embolism in a vessel was seen. In the endometrium the squamous carcinoma had collided with a hyperplastic endometrium, focally with severe atypical hyperplasia. There was no sign of invasive endometrial carcinoma. In the cystic part of the right ovary the epithelium was stratified, with layers of atypical cells which showed areas o f a cribriform glandular pattern and epithelial protrusions. warranting the diagnosis of a cystadenoma of borderline malignancy. N o stromal invasion was found. In one part o f the atypical epithelium of the cyst an invasively growing area of squamous carcinoma was localized, the latter morphologically identical with the cervical carcinoma (Fig. 1 ) .
McCall et al. (6) pioneered the concept o f ovarian conservation in cases of surgery of low-stage carcinoma of the cervix. Their rcsults have been confirmed by others (1.2) who found no metastases to the ovaries from low-stage cervical carcinoma. In a review of the literature we have found reports on 3 cases of metastases t o the ovary from low-stagc carcinoma of the cervix (7,8,9). The first was a glassy cell carcinoma with metastases to pelvic lymph nodes. This carcinoma is perhaps more aggressive in nature than the pure squamous carcinoma (10). In the second case the metastasis to thc ovary was found 13 months postoperatively and there was spreading to pelvic peritoneum. In the third case there was spreading of tumor to the pelvic lymph nodes. Fdbata et al. (1) found at autopsy on more advanced cases of cervical carcinoma an increasing tendency to metastasize to the ovary in cases of spreading to the uterine corpus. The overall incidence of metastasis to the ovary is highest in young patients, presumably because the ovary in this age group is more richly vascularized and therefore more susceptible to hematogenous spread (10). In our case, where the spread had occurred early, there was spread to the endometrium. but no metastases to the regional lymph nodes. The metastasis in the ovary was located in a borderline cystadenoma with o n sign of stromal invasion. The location of the metastasis and the presence of a tumor embolus in a myometrial vessel support our conclusion that it was a true metastasis and not a primary ovarian tumor. The route of spreading of the squamous carcinoma to the ovary was most likely hematogenous. Metastasis from neoplasm to neoplasm is rare but has been reported in a number of cases, with the majority of the metastases being to another malignant tumor. The dissemination of the donor tumors was in most cases extensive. Breast and bronchogenic cancers constitute the majority of the cancers which metastazise to other tumors, but it is tumors in the kidney which are hosts to the metastasizing tumors in most of the reported cases ( 5 ) . Several explanations for the apparent preference for tumors of the kidney have been proposed: the copious blood flow to the kidney and local factors within the renal cell tumor facilitating growth of the metastasizing tumor cells (1 1). As noted by others, care should be taken to ensure that the metastasis to another tumor is a true metastasis and not a tumor collision of two adjacent primary tumors or a static embolus with no sign of invasive growth ( 1 1). Our patient had, in addition to the metastasizing
Metastusk to the ovury
squamous carcinoma of the cervix, concomitant premalignant lesions in the endometrium and ovary. This could lead to pathogenetic considerations, since it appears that the entire epithelial surface of the upper genital tract is prcdisposed to malignant transformation. The structures of the upper genital tract have a common embryological origin and may respond in a similar manner to local carcinogenic influence. The prognosis in synchronous carcinomas of the uterus and ovaries seems relatively good, with invasion in the endometrium as a prognostic factor
(3. Our patient who had early ovarian metastasis from a squamous carcinoma o f the cervix emphasizes the need for careful exmination of the ovaries in cases of surgery. However, reports on ovarian metastasis in low-stage squamous carcinoma of the ccrvix are few and it still seems justified to spare the ovarics at surgery on thc young patient, though perhaps tumor spread to the endometrium or myometrium should lead to reconsideration of removal of the ovaries.
71
3. Zaino RJ, Unger E R , Whitney C. Synchronous carcinomas of the uterine corpus and ovary. Gynccol Oncol 1084; 19: 329-35. 4. Deligdisch L, Szulman A . Multiple and multifocal carcinomas in the female genital organs and breast. Gynecol Oncol 1975; 3: 181-90. 5. Seitz G , Schuder G. Neoplasm t o neoplasm metastasis Pheochromocytoma harboring a metastasis of breast cancer. Path Res Pract 1987; 182: 228-32. 6. MacCall ML, Keaty EC, Thompson J D . Conservation of ovarian tissue in the treatment of carcinoma of the cervix with radical surgery. A m J Obstet Gynecol 1958; 75: 590-604. 7. Nahhas WA, Abt AB, Mortel R . Stage 1B glassy cell carcinoma of the cervix ovarian metastases. Gynecol Oncol 1977; 5: 87-91. 8. Cassidy LJ. Kennedy J H . Ovarian metastasis from stage 1B carcinoma of the cervix. Case report. Br J Ohstet Gynaecol 1986; 93: 1169-70. 9. Johnston G A , Clausen K. Early stage carcinoma of the cervix complicating pregnancy with metastases to an ovarian endometrioma. J Rcprod Med 1982; 27: 372-2. 10. Young HY, Scully R E . Metastatic tumors of the ovary. In: Blaustein’s pathology of the female genital tract. New York: Springer-Verlag, 1987; 743-68. 11. Singh EO, Benson RC, Wold LE. Cancer-to-cancer metastasis. J. Urol 1984; 132: 34(k2.
References 1. Tahata M, lchinoc K, Sakuragi N, Shiina Y, Yamaguchi T. Mabuchi Y. lncidencc of ovarian metastasis in
patients with cancer of thc uterine cervix. Gynecol Oncol 1987; 28; 255-61. 2. Webb G A . The role of ovarian conservation in the treatment o f carcinoma of the cervix with radical surgcry. Am J Obstct Gynecol 1975; 122: 47684.
Address for correspondence:
Roar B. Rasmussen, M.D. Immerkaer 30D DK-2650 Hvidovre Denmark
Acra Obster Gynecol Scund 71 (1YYZJ
Metastasis from squamous carcinoma of the cervix stage 1B to a borderline cystadenoma of the ovary ROARBRUUNRASMUSSEN’, BIRGITTEBRUUNRASMUSSEN‘ AND JENSB. KNUDSEN’
From the ‘Department of Gynecology & Obstetrics and t h e ‘Department of Pathology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
Acta Obstst Gynecol Scand 1992; 71: 69-71 A case of metastasis from squamous carcinoma stage 1B of the cervix to a borderline cystadenoma of the ovary is described. In addition, the patient had atypical endometrial
hyperplasia. The patient underwent a radical hysterectomy with no adjuvant postoperative treatment and has resumed work, with no sign of recurrence one year postoperatively. The aspects of the metastasis to the ovary, multiple tumors in the genital tract and tumor-to-tumor metastasis are discussed. Reports on ovarian metastasis in low-stage squamous carcinoma of the cervix are few and it still seems justified to spare the ovaries at surgery in the young patient. Key words: carcinoma of the cervix; squamous carcinoma; ovarian metastasis Submitted Januury 10, 1991 Accepted August 29, 1991
Metastasis to the ovary in cases of squamous carcinoma of the cervix is rare (1,2). There is a general consensus to avoid removing the ovaries at surgery for low-stage squamous cervical carcinoma in young females in order to preserve the endocrine function and avoid menopausal symptoms (1,2). Synchronous neoplasms of the ovary and uterus are an uncommon but well known entity with a reported incidence of less than 1% of all forms of cancer in the upper genital tract (3,4). Metastasis from one neoplasm to another tumor, whether malignant, premalignant or benign, is a rare event, but has been reported in a number of cases (5). We report a case of squamous carcinoma of the cervix with metastasis to a borderline cystadenoma of the ovary in a patient who in addition had atypical endometrial hyperplasia.
Case report A 54-year-old previously healthy female, was referred with vaginal bleeding of 3 months’ duration. She had never received hormonal treatment and had no family history of malignant disease. A t examination, a tumor protruding from the orifice of an enlarged cervix was found. The uterus was enlarged but mobile and the adnexa were unremarkable. The patient underwent cervical biopsy and curettage of the uterus, which revealed invasive squamous carcinoma of the cervix and growth of squamous carcinoma in the endometrium and endocervix. The tumor was classified as stage 1B. The patient underwent a radical hysterectomy, bilateral salpingo-oophorectomy, pelvic lymphadenectomy and appendectomy. At the time of operation the right ovary appeared to have small cysts and the left ovary appeared atrophic. The uterus was enlarged but there was no sign of tumor penetration. The patient received no postoperative adjuvant Acru Ohstrt Gynrrol Stand 71 (IYY2)
70
R. B. Rusmussen et ul.
Discussion
Fig. I . Ovary with serous cystadenoma. borderline typc of the cervix (crrrowhud). I harr = 20pm. (crrrow) and metastatic squamous carcinoma
treatment. Two months postoperatively she was referred twice to the regional hospital presenting with mild symptoms of ileus which was managed conservatively. Since then she has been well and is now, one year after surgery, free from signs of recurrence and has resumed work.
Pathologic findings The utcrus was found to be enlarged due t o a 9 X 7 cm tumor involving thc cervix and isthmus and which had spread to the uterine corpus posteriorly. There were no macroscopic signs o f tumor spread to the surface o f the uterus. The specimen included a right-side ovary measuring 3.5 x 2 x 1 cm, with several cysts. Microscopically the tumor consisted of an invasive keratinizing squamous carcinoma. It had involved thc isthmus and was spreading to the endometrium, hut had not yet penetrated the serosal surface. There was spread to the myometrium and in one section a tumor embolism in a vessel was seen. In the endometrium the squamous carcinoma had collided with a hyperplastic endometrium, focally with severe atypical hyperplasia. There was no sign of invasive endometrial carcinoma. In the cystic part of the right ovary the epithelium was stratified, with layers of atypical cells which showed areas o f a cribriform glandular pattern and epithelial protrusions. warranting the diagnosis of a cystadenoma of borderline malignancy. N o stromal invasion was found. In one part o f the atypical epithelium of the cyst an invasively growing area of squamous carcinoma was localized, the latter morphologically identical with the cervical carcinoma (Fig. 1 ) .
McCall et al. (6) pioneered the concept o f ovarian conservation in cases of surgery of low-stage carcinoma of the cervix. Their rcsults have been confirmed by others (1.2) who found no metastases to the ovaries from low-stage cervical carcinoma. In a review of the literature we have found reports on 3 cases of metastases t o the ovary from low-stagc carcinoma of the cervix (7,8,9). The first was a glassy cell carcinoma with metastases to pelvic lymph nodes. This carcinoma is perhaps more aggressive in nature than the pure squamous carcinoma (10). In the second case the metastasis to thc ovary was found 13 months postoperatively and there was spreading to pelvic peritoneum. In the third case there was spreading of tumor to the pelvic lymph nodes. Fdbata et al. (1) found at autopsy on more advanced cases of cervical carcinoma an increasing tendency to metastasize to the ovary in cases of spreading to the uterine corpus. The overall incidence of metastasis to the ovary is highest in young patients, presumably because the ovary in this age group is more richly vascularized and therefore more susceptible to hematogenous spread (10). In our case, where the spread had occurred early, there was spread to the endometrium. but no metastases to the regional lymph nodes. The metastasis in the ovary was located in a borderline cystadenoma with o n sign of stromal invasion. The location of the metastasis and the presence of a tumor embolus in a myometrial vessel support our conclusion that it was a true metastasis and not a primary ovarian tumor. The route of spreading of the squamous carcinoma to the ovary was most likely hematogenous. Metastasis from neoplasm to neoplasm is rare but has been reported in a number of cases, with the majority of the metastases being to another malignant tumor. The dissemination of the donor tumors was in most cases extensive. Breast and bronchogenic cancers constitute the majority of the cancers which metastazise to other tumors, but it is tumors in the kidney which are hosts to the metastasizing tumors in most of the reported cases ( 5 ) . Several explanations for the apparent preference for tumors of the kidney have been proposed: the copious blood flow to the kidney and local factors within the renal cell tumor facilitating growth of the metastasizing tumor cells (1 1). As noted by others, care should be taken to ensure that the metastasis to another tumor is a true metastasis and not a tumor collision of two adjacent primary tumors or a static embolus with no sign of invasive growth ( 1 1). Our patient had, in addition to the metastasizing
Metastusk to the ovury
squamous carcinoma of the cervix, concomitant premalignant lesions in the endometrium and ovary. This could lead to pathogenetic considerations, since it appears that the entire epithelial surface of the upper genital tract is prcdisposed to malignant transformation. The structures of the upper genital tract have a common embryological origin and may respond in a similar manner to local carcinogenic influence. The prognosis in synchronous carcinomas of the uterus and ovaries seems relatively good, with invasion in the endometrium as a prognostic factor
(3. Our patient who had early ovarian metastasis from a squamous carcinoma o f the cervix emphasizes the need for careful exmination of the ovaries in cases of surgery. However, reports on ovarian metastasis in low-stage squamous carcinoma of the ccrvix are few and it still seems justified to spare the ovarics at surgery on thc young patient, though perhaps tumor spread to the endometrium or myometrium should lead to reconsideration of removal of the ovaries.
71
3. Zaino RJ, Unger E R , Whitney C. Synchronous carcinomas of the uterine corpus and ovary. Gynccol Oncol 1084; 19: 329-35. 4. Deligdisch L, Szulman A . Multiple and multifocal carcinomas in the female genital organs and breast. Gynecol Oncol 1975; 3: 181-90. 5. Seitz G , Schuder G. Neoplasm t o neoplasm metastasis Pheochromocytoma harboring a metastasis of breast cancer. Path Res Pract 1987; 182: 228-32. 6. MacCall ML, Keaty EC, Thompson J D . Conservation of ovarian tissue in the treatment of carcinoma of the cervix with radical surgery. A m J Obstet Gynecol 1958; 75: 590-604. 7. Nahhas WA, Abt AB, Mortel R . Stage 1B glassy cell carcinoma of the cervix ovarian metastases. Gynecol Oncol 1977; 5: 87-91. 8. Cassidy LJ. Kennedy J H . Ovarian metastasis from stage 1B carcinoma of the cervix. Case report. Br J Ohstet Gynaecol 1986; 93: 1169-70. 9. Johnston G A , Clausen K. Early stage carcinoma of the cervix complicating pregnancy with metastases to an ovarian endometrioma. J Rcprod Med 1982; 27: 372-2. 10. Young HY, Scully R E . Metastatic tumors of the ovary. In: Blaustein’s pathology of the female genital tract. New York: Springer-Verlag, 1987; 743-68. 11. Singh EO, Benson RC, Wold LE. Cancer-to-cancer metastasis. J. Urol 1984; 132: 34(k2.
References 1. Tahata M, lchinoc K, Sakuragi N, Shiina Y, Yamaguchi T. Mabuchi Y. lncidencc of ovarian metastasis in
patients with cancer of thc uterine cervix. Gynecol Oncol 1987; 28; 255-61. 2. Webb G A . The role of ovarian conservation in the treatment o f carcinoma of the cervix with radical surgcry. Am J Obstct Gynecol 1975; 122: 47684.
Address for correspondence:
Roar B. Rasmussen, M.D. Immerkaer 30D DK-2650 Hvidovre Denmark
Acra Obster Gynecol Scund 71 (1YYZJ
