GYNECOLOGIC
ONCOLOGY
39, 221-224 (I!%@
CASE REPORT Papillary Villoglandular Carcinoma of the Cervix LILA HOPSON, B.A.,* MICHAEL A. JONES, M.D.,t CHARLES R. BOYCE, M.D. ,* AND HECTOR M. TARRAZA, JR., M.D.*,’ Departments of *Obstetrics and Gynecology and tPathology, Maine Medical Center, Portland, Maine 04102
Received May 10, 1990 Three casesof papillary villoglandular carcinoma of the cervix are presented. Each patient was multiparous and presented with abnormal vaginal bleeding. The mean age at presentation was 35 years (range 28-42 years). All patients were staged as FIG0 IB and underwent radical Wertheim hysterectomy and bilateral pelvic lymphadenectomy. Disease was lhnited to the cervix in two patients and extended to involve the lower uterine segment in one patient. There was no evidence of microscopic spread to the lymph nodes. Previous reports that examined patients with papillary v&glandular carcinoma of the cervix found them to have a favorable prognosis. Treatment implications are discussed. 0 1990 Academic
Rap.
Although opinions vary, in general adenocarcinoma of the cervix has been associated with a poorer prognosis than invasive squamous cell carcinoma of the cervix [1,3,6,8]. With the excellent prognosis accorded to the papillary villoglandular carcinoma by Young and Scully [l], recognition of the entity and separation from other forms of endocervical adenocarcinoma are important. We have recently encountered three cases of papillary villoglandular adenocarcinoma. The clinicopathologic features of the tumor as well as prognostic and treatment implications are discussed.
Inc.
CASE REPORTS INTRODUCTION
Case I Adenocarcinoma of the uterine cervix accounts for IO20% of all cervical carcinomas [l-6]. Although much has been written about adenocarcinoma of the cervix, limited information is available on the various histologic subtypes of this tumor. Recently, Young and Scully [ 11drew attention to the papillary villoglandular subtype, a relatively uncommon form of well-differentiated endocervical adenocarcinoma. The actual incidence of the papillary villoglandular subtype is unknown. Undoubtedly, examples of this tumor type have been nonspecifically included in the welldifferentiated category in previous reports [2-71, while in other reviews it may have been included (along with serous and clear cell subtypes) in the category of papillary adenocarcinoma. As pointed out by Young and Scully [ 11,the latter category accounts for approximately lo- 15% of cervical adenocarcinomas and thus one would estimate the incidence of papillary villoglandular neoplasms as something less than this figure.
A 38-year-old white female, gravida 3, para 2, spontaneous abortion 2, presented with postcoital bleeding since a spontaneous abortion 2 months prior to admission. Examination revealed a small 1.5cm lesion on the anterior lip of the cervix. Pap smear was suspicious for an adenocarcinoma. Cervical biopsy showed a well-differentiated endocervical papillary villoglandular adenocarcinoma. Intravenous pyelogram was normal. Chest X ray showed no evidence of disease. Examination under anesthesia revealed the presence of cervical tumor with no paracervical or parametrial involvement. Sigmoidoscopy and cystoscopy were normal. She was staged as FIG0 IB. The patient underwent a radical Wertheim hysterectomy and bilateral pelvic lymphadenectomy. She had an uneventful recovery and 8 months later is free of disease. Case 2 A 42-year-old white female, gravida 3, para 3, pre-
’ To whom correspondence should be addressed.
sented with a l-year history
of vaginal discharge and 6
221 oo!xL8258/90 $1.50 Copyright 0 1990by AcademicPress,Inc. All rights of reproductionin any form reserved.
222
HOPSON ET AL.
FIG. 1. Gross appearance of papillary villoglandular carcinoma of the cervix. Well-circumscribed margins of the tumor (arrows) invade the underlying cervical wall.
weeks of postcoital bleeding. Abnormal cervical cytology (suspicious for adenocarcinoma) was followed by endocervical curettings positive for papillary villoglandular adenocarcinoma. An MRI revealed a 3.O-cm well-defined mass within the uterine cervix without evidence of extension or pelvic metastasis. Chest X ray and intravenous pyelogram were normal. Examination under anesthesia revealed a slightly enlarged cervix with no evidence of paracervical or parametrial involvement. She was staged as FIG0 IB. She underwent a radical Wertheim hysterectomy and bilateral pelvic lymphadenectomy. The patient had an uneventful recovery and at 8 months following her surgery shows no evidence of disease. Case 3 A 28-year-old white female, gravida 2, para 2, presented with a 6-month history of midcycle spotting and 3 months of lower abdominal pain. Abnormal cervical cytology (suspicious for adenocarcinoma) was followed by endocervical curettings and a cervical biopsy, both positive for papillary villoglandular adenocarcinoma. Abdominal CT scan showed no masses or evidence of disease. Chest X ray and intravenous pyelogram were normal. Examination under anesthesia revealed a small, l-cm anterior cervical erosion with no paracervical or parametrial involvement. Cystoscopy and proctoscopy were normal. She was staged as FIG0 IB. The patient underwent a radical Wertheim hysterectomy and bilateral pelvic lymphadenectomy. The patient had an uneventful hospital course.
PATHOLOGIC FINDINGS Gross Features All of the tumors produced grossly visible lesions (Fig. 1) and were usually described as exophytic, friable masses protruding from the cervical wall. In addition to the exophytic component, all tumors contained an endophytic or excavated portion, well demonstrated on perpendicular sections of the cervix. In one case an abundant mucoid discharge was present on the tumor surface. In case 2, the tumor measured 3.5 cm and penetrated deep into the cervical wall extending through 75% of its total thickness. Extension to the lower uterine segment was present as well. In case 1 the tumor was 2.5 cm in maximal diameter and in case 3 it measured 2 cm. Microscopic Features The superficial, exophytic portions of the tumor were composed of variably sized papillary and villous fibrovascular fronds (Fig. 2). The deep, infiltrative component, in addition to the above architecture, featured elongated, branching glandular structures. The villous component of the tumors was similar in appearance to villous adenoma of the colon. Papillary and villous structures were lined by stratified columnar cells which generally lacked mucin secretion although occasional mutinous foci were noted in all three tumors. Nuclear atypia was mild to moderate. Occasional mitotic activity was noted in all cases. A prominent desmoplastic and inflammatory tumor response characterized the advancing margin of the tumors. In one case (Fig. 3), a small focus of invasive,
223
CASE REPORT
FIG. 2. Microscopic section of papillary villoglandular carcinoma of the cervix. Fibrovascular villi lined by nonmucinous columnar cells. H&E, x 16.
well-differentiated squamous cell carcinoma was associated with the typical papillary villoglandular component. No tumor demonstrated vascular or lymphatic space involvement. All tumors were considered grade 1. No glandular or squamous in situ component was identified. The tumors in cases 2 and 3 were confined to the inner one-third of the cervical wall, while in case 3 extension through 75% of the total thickness was present. Pathologic examination of right and left pelvic lymph nodes was negative for tumor in all cases.
DISCUSSION Papillary villoglandular adenocarcinoma of the cervix is rare, and the first clinicopathologic analysis of this histologic subtype was only recently published [l]. Previous reports of cervical adenocarcinoma have either not discussed it at all or, more likely, have included it with other lesions in the papillary or well-differentiated categories. In previous series papillary adenocarcinoma has represented from 10 to 15% of all cervical adenocarci-
FIG. 3. Focus of well-differentiated squamous cell carcinoma (left side) adjacent to otherwise typical papillary villoglandular carcinoma of the cervix (right side). H&E, x6.3.
224
HOPSON ET AL.
noma, but as pointed out by Young and Scully [l] this includes serous and clear cell subtypes. The actual incidence of papillary villoglandular adenocarcinoma of the cervix is thus likely less. Recognition of this subtype and its inclusion in subsequent larger series of cervical adenocarcinoma will allow for better estimates of its true incidence. The three cases of a papillary villoglandular adenocarcinoma of the cervix in this series were similar in age, presentation, and parity to those reported by Young and Scully. All of our patients were premenopausal with a mean age of 35 years, which is younger than that reported for patients with cervical adenocarcinoma of other subtypes [24X]. All three women were multiparous and had abnormal vaginal bleeding as their presenting symptom, similar to other patients with cervical adenocarcinoma. It is noteworthy that all three of our patients had previous tubal ligations. Although there have been reports of an association between oral contraceptive use and cervical adenocarcinoma no specific association has been drawn between a patient’s reproductive function and cervical adenocarcinoma. All three patients underwent a radical Wertheim hysterectomy and bilateral pelvic lymphadenectomy and all lymph nodes and cervical margins were free of disease. One patient had deep cervical wall invasion with involvement of a lower uterine segment; one had invasion to less than 50% of the cervical wall thickness and one had invasion to less than 35% of the cervical wall thickness. Cervical biopsies obtained prior to definitive surgery were not predictive of the actual amount of invasion documented on hysterectomy specimens. Young and Scully have suggested that in light of the good prognosis for patients with this subtype of adenocarcinoma a conservative procedure (with preservation of reproductive
function) should be considered in selective cases and that a cone biopsy may serve as the initial therapy of choice, unless the tumor has been shown by the biopsy to be more than microinvasive. They further suggest that if the margins of the cone are clear of disease with no more than a 3-mm depth of invasion and no lymphvascular space involvement, it appears justifiable to perform no additional treatment and follow the patient carefully. This protocol was not followed in these cases, because of the size of the tumor. In patients who do not meet the above criteria, it is still advisable to perform radical surgery in operative candidates in light of the excellent results previously seen with this treatment. REFERENCES 1. Young, R., and Scully, R. Villoglandular papillary adenocarcinoma of the uterine cervix, Cancer 63, 1773-1779 (1989). 2. Ireland, D., Hardiman, P., and Monaghan, J. Adenocarcinoma of the uterine cervix: A study of 73 cases, Obstet. Gynecol. 65, 8285 (1985). 3. Gallup, D., and Abell, M. Invasive adenocarcinoma of the uterine cervix, Obstet. Gynecol. 49, 5%-603 (1977). 4. Anderson, M. C., and Fraser, A. C. Adenocarcinoma of the uterine cervix: A clinical and pathological appraisal, &it. J. Obstet. Gynecol. 83, 320-325 (1976). 5. Hepler, T., Dockerty, M., and Randall, L. Primary adenocarcinoma of the cervix, Amer. J. Obstet. Gynecol. 63, 800-808 (1952). 6. Rombaut, R., Charles, D., and Murphy, A. Adenocarcinoma of the cervix: A clinicopathologic study of 47 cases, Cancer 19, 891-900 Wm. Abell, M., and Gosling, J. Gland cell carcinoma (adenocarcinoma) of the uterine cervix, Amer. J. Obstet. Gynecol. 83,729-755 (1962). Fu, Y., Reagan, J., Hsiu, J., Storaasi, J., and Wentz, W. Adenocarcinoma and mixed carcinoma of the uterine cervix, Cancer 49, 2560-2570 (1982). Marcus, S., and Marcus, C. Primary adenocarcinoma of the cervix uteri, Amer. J. Obstet. Gynecol. 86, 384-3% (1%3).
ONCOLOGY
39, 221-224 (I!%@
CASE REPORT Papillary Villoglandular Carcinoma of the Cervix LILA HOPSON, B.A.,* MICHAEL A. JONES, M.D.,t CHARLES R. BOYCE, M.D. ,* AND HECTOR M. TARRAZA, JR., M.D.*,’ Departments of *Obstetrics and Gynecology and tPathology, Maine Medical Center, Portland, Maine 04102
Received May 10, 1990 Three casesof papillary villoglandular carcinoma of the cervix are presented. Each patient was multiparous and presented with abnormal vaginal bleeding. The mean age at presentation was 35 years (range 28-42 years). All patients were staged as FIG0 IB and underwent radical Wertheim hysterectomy and bilateral pelvic lymphadenectomy. Disease was lhnited to the cervix in two patients and extended to involve the lower uterine segment in one patient. There was no evidence of microscopic spread to the lymph nodes. Previous reports that examined patients with papillary v&glandular carcinoma of the cervix found them to have a favorable prognosis. Treatment implications are discussed. 0 1990 Academic
Rap.
Although opinions vary, in general adenocarcinoma of the cervix has been associated with a poorer prognosis than invasive squamous cell carcinoma of the cervix [1,3,6,8]. With the excellent prognosis accorded to the papillary villoglandular carcinoma by Young and Scully [l], recognition of the entity and separation from other forms of endocervical adenocarcinoma are important. We have recently encountered three cases of papillary villoglandular adenocarcinoma. The clinicopathologic features of the tumor as well as prognostic and treatment implications are discussed.
Inc.
CASE REPORTS INTRODUCTION
Case I Adenocarcinoma of the uterine cervix accounts for IO20% of all cervical carcinomas [l-6]. Although much has been written about adenocarcinoma of the cervix, limited information is available on the various histologic subtypes of this tumor. Recently, Young and Scully [ 11drew attention to the papillary villoglandular subtype, a relatively uncommon form of well-differentiated endocervical adenocarcinoma. The actual incidence of the papillary villoglandular subtype is unknown. Undoubtedly, examples of this tumor type have been nonspecifically included in the welldifferentiated category in previous reports [2-71, while in other reviews it may have been included (along with serous and clear cell subtypes) in the category of papillary adenocarcinoma. As pointed out by Young and Scully [ 11,the latter category accounts for approximately lo- 15% of cervical adenocarcinomas and thus one would estimate the incidence of papillary villoglandular neoplasms as something less than this figure.
A 38-year-old white female, gravida 3, para 2, spontaneous abortion 2, presented with postcoital bleeding since a spontaneous abortion 2 months prior to admission. Examination revealed a small 1.5cm lesion on the anterior lip of the cervix. Pap smear was suspicious for an adenocarcinoma. Cervical biopsy showed a well-differentiated endocervical papillary villoglandular adenocarcinoma. Intravenous pyelogram was normal. Chest X ray showed no evidence of disease. Examination under anesthesia revealed the presence of cervical tumor with no paracervical or parametrial involvement. Sigmoidoscopy and cystoscopy were normal. She was staged as FIG0 IB. The patient underwent a radical Wertheim hysterectomy and bilateral pelvic lymphadenectomy. She had an uneventful recovery and 8 months later is free of disease. Case 2 A 42-year-old white female, gravida 3, para 3, pre-
’ To whom correspondence should be addressed.
sented with a l-year history
of vaginal discharge and 6
221 oo!xL8258/90 $1.50 Copyright 0 1990by AcademicPress,Inc. All rights of reproductionin any form reserved.
222
HOPSON ET AL.
FIG. 1. Gross appearance of papillary villoglandular carcinoma of the cervix. Well-circumscribed margins of the tumor (arrows) invade the underlying cervical wall.
weeks of postcoital bleeding. Abnormal cervical cytology (suspicious for adenocarcinoma) was followed by endocervical curettings positive for papillary villoglandular adenocarcinoma. An MRI revealed a 3.O-cm well-defined mass within the uterine cervix without evidence of extension or pelvic metastasis. Chest X ray and intravenous pyelogram were normal. Examination under anesthesia revealed a slightly enlarged cervix with no evidence of paracervical or parametrial involvement. She was staged as FIG0 IB. She underwent a radical Wertheim hysterectomy and bilateral pelvic lymphadenectomy. The patient had an uneventful recovery and at 8 months following her surgery shows no evidence of disease. Case 3 A 28-year-old white female, gravida 2, para 2, presented with a 6-month history of midcycle spotting and 3 months of lower abdominal pain. Abnormal cervical cytology (suspicious for adenocarcinoma) was followed by endocervical curettings and a cervical biopsy, both positive for papillary villoglandular adenocarcinoma. Abdominal CT scan showed no masses or evidence of disease. Chest X ray and intravenous pyelogram were normal. Examination under anesthesia revealed a small, l-cm anterior cervical erosion with no paracervical or parametrial involvement. Cystoscopy and proctoscopy were normal. She was staged as FIG0 IB. The patient underwent a radical Wertheim hysterectomy and bilateral pelvic lymphadenectomy. The patient had an uneventful hospital course.
PATHOLOGIC FINDINGS Gross Features All of the tumors produced grossly visible lesions (Fig. 1) and were usually described as exophytic, friable masses protruding from the cervical wall. In addition to the exophytic component, all tumors contained an endophytic or excavated portion, well demonstrated on perpendicular sections of the cervix. In one case an abundant mucoid discharge was present on the tumor surface. In case 2, the tumor measured 3.5 cm and penetrated deep into the cervical wall extending through 75% of its total thickness. Extension to the lower uterine segment was present as well. In case 1 the tumor was 2.5 cm in maximal diameter and in case 3 it measured 2 cm. Microscopic Features The superficial, exophytic portions of the tumor were composed of variably sized papillary and villous fibrovascular fronds (Fig. 2). The deep, infiltrative component, in addition to the above architecture, featured elongated, branching glandular structures. The villous component of the tumors was similar in appearance to villous adenoma of the colon. Papillary and villous structures were lined by stratified columnar cells which generally lacked mucin secretion although occasional mutinous foci were noted in all three tumors. Nuclear atypia was mild to moderate. Occasional mitotic activity was noted in all cases. A prominent desmoplastic and inflammatory tumor response characterized the advancing margin of the tumors. In one case (Fig. 3), a small focus of invasive,
223
CASE REPORT
FIG. 2. Microscopic section of papillary villoglandular carcinoma of the cervix. Fibrovascular villi lined by nonmucinous columnar cells. H&E, x 16.
well-differentiated squamous cell carcinoma was associated with the typical papillary villoglandular component. No tumor demonstrated vascular or lymphatic space involvement. All tumors were considered grade 1. No glandular or squamous in situ component was identified. The tumors in cases 2 and 3 were confined to the inner one-third of the cervical wall, while in case 3 extension through 75% of the total thickness was present. Pathologic examination of right and left pelvic lymph nodes was negative for tumor in all cases.
DISCUSSION Papillary villoglandular adenocarcinoma of the cervix is rare, and the first clinicopathologic analysis of this histologic subtype was only recently published [l]. Previous reports of cervical adenocarcinoma have either not discussed it at all or, more likely, have included it with other lesions in the papillary or well-differentiated categories. In previous series papillary adenocarcinoma has represented from 10 to 15% of all cervical adenocarci-
FIG. 3. Focus of well-differentiated squamous cell carcinoma (left side) adjacent to otherwise typical papillary villoglandular carcinoma of the cervix (right side). H&E, x6.3.
224
HOPSON ET AL.
noma, but as pointed out by Young and Scully [l] this includes serous and clear cell subtypes. The actual incidence of papillary villoglandular adenocarcinoma of the cervix is thus likely less. Recognition of this subtype and its inclusion in subsequent larger series of cervical adenocarcinoma will allow for better estimates of its true incidence. The three cases of a papillary villoglandular adenocarcinoma of the cervix in this series were similar in age, presentation, and parity to those reported by Young and Scully. All of our patients were premenopausal with a mean age of 35 years, which is younger than that reported for patients with cervical adenocarcinoma of other subtypes [24X]. All three women were multiparous and had abnormal vaginal bleeding as their presenting symptom, similar to other patients with cervical adenocarcinoma. It is noteworthy that all three of our patients had previous tubal ligations. Although there have been reports of an association between oral contraceptive use and cervical adenocarcinoma no specific association has been drawn between a patient’s reproductive function and cervical adenocarcinoma. All three patients underwent a radical Wertheim hysterectomy and bilateral pelvic lymphadenectomy and all lymph nodes and cervical margins were free of disease. One patient had deep cervical wall invasion with involvement of a lower uterine segment; one had invasion to less than 50% of the cervical wall thickness and one had invasion to less than 35% of the cervical wall thickness. Cervical biopsies obtained prior to definitive surgery were not predictive of the actual amount of invasion documented on hysterectomy specimens. Young and Scully have suggested that in light of the good prognosis for patients with this subtype of adenocarcinoma a conservative procedure (with preservation of reproductive
function) should be considered in selective cases and that a cone biopsy may serve as the initial therapy of choice, unless the tumor has been shown by the biopsy to be more than microinvasive. They further suggest that if the margins of the cone are clear of disease with no more than a 3-mm depth of invasion and no lymphvascular space involvement, it appears justifiable to perform no additional treatment and follow the patient carefully. This protocol was not followed in these cases, because of the size of the tumor. In patients who do not meet the above criteria, it is still advisable to perform radical surgery in operative candidates in light of the excellent results previously seen with this treatment. REFERENCES 1. Young, R., and Scully, R. Villoglandular papillary adenocarcinoma of the uterine cervix, Cancer 63, 1773-1779 (1989). 2. Ireland, D., Hardiman, P., and Monaghan, J. Adenocarcinoma of the uterine cervix: A study of 73 cases, Obstet. Gynecol. 65, 8285 (1985). 3. Gallup, D., and Abell, M. Invasive adenocarcinoma of the uterine cervix, Obstet. Gynecol. 49, 5%-603 (1977). 4. Anderson, M. C., and Fraser, A. C. Adenocarcinoma of the uterine cervix: A clinical and pathological appraisal, &it. J. Obstet. Gynecol. 83, 320-325 (1976). 5. Hepler, T., Dockerty, M., and Randall, L. Primary adenocarcinoma of the cervix, Amer. J. Obstet. Gynecol. 63, 800-808 (1952). 6. Rombaut, R., Charles, D., and Murphy, A. Adenocarcinoma of the cervix: A clinicopathologic study of 47 cases, Cancer 19, 891-900 Wm. Abell, M., and Gosling, J. Gland cell carcinoma (adenocarcinoma) of the uterine cervix, Amer. J. Obstet. Gynecol. 83,729-755 (1962). Fu, Y., Reagan, J., Hsiu, J., Storaasi, J., and Wentz, W. Adenocarcinoma and mixed carcinoma of the uterine cervix, Cancer 49, 2560-2570 (1982). Marcus, S., and Marcus, C. Primary adenocarcinoma of the cervix uteri, Amer. J. Obstet. Gynecol. 86, 384-3% (1%3).
