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Widespread lymph node metastases in a patient with microinvasive cervical carcinoma
GYNECOLOGIC
ONCOLOGY
34,
219-221 (1989)
CASE REPORT Widespread Lymph Node Metastases in a Patient with Microinvasive Cervical Carcinoma’ HARRY S. COLLINS, MAJ. M.C. U.S.A., THOMAS W. BURKE, MAJ. M.C. U.S.A. ,* JOAN E. WOODWARD, MAJ. M.C. U.S.A., JOHN W. SPURLOCK,CPT. M.C. U.S.A., AND PAUL B. HELLER, COL. M.C. U.S.A. Gynecologic
Oncology
and Pathology
Services,
Walter Reed Army Medical
Center, Washington,
D.C. 20307-5001
Received April 26, 1988
Lymph node metastasis is uncommon in patients with microinvasive squamous cell carcinoma of the cervix and is particularly unusual in tumors with early stromal invasion. We describe a patient with maxhnum stromal invasion of 0.8 mm who had extensive pelvic and para-aortic nodal metastasesdiscovered at laparotomy. Despite combined modality therapy, she died with progressive disease. New clinical staging definitions for Stage IA cervical carcinoma incorporate measurement of both depth of invasion and lateral tumor spread and have resolved many of the descriptive controversies surrounding this entity., Our case illustrates that any degree of stromal invasion carries some risk of nodal metastasis. The management of patients with microinvasive carcinoma should be individualized. An abdominal approach should be considered for patients being treated by extrafascial hysterectomy to allow assessmentof the regional lymph nodes. Whether more aggressive therapy will hrfluence the outcome for the rare patient with lymph node metastasis is unknown. 8 19ag Academic I’rcss, Inc.
Microinvasive squamous cell carcinoma of the cervix is normally characterized by a low incidence of lymph node metastasis and an excellent prognosis [l-8]. Lymph node metastasis has been particularly uncommon in tumors with early stromal invasion [1,3,4,6-81 or small volume [2,5]. This report describes a patient with minimally invasive (
CASE HISTORY A 33-year-old black gravida 4 para 4 was referred to Walter Reed Army Medical Center after a cone biopsy demonstrated microinvasive squamous cell carcinoma of the cervix. Colposcopic evaluation for an abnormal Papanicolaou smear 15 months earlier had shown CIN III with a positive endocervical curettage. She refused recommended cone biopsy and was not seen until 3 months prior to referral. Repeat colposcopic examination with biopsies demonstrated CIN III with dysplastic epithelium present in endocervical curettings. She again delayed diagnostic cone biopsy but was finally persuaded to undergo the procedure. Histologic review of multiple sections and step sections from the cone biopsy specimen confirmed the diagnosis of microinvasive squamous cell carcinoma. Several sites of early stromal invasion were seen in sections from a single tissue block. All but one of these were small buds of invasive tumor extending ~0.2 mm from the basement membrane (Fig. 1). The area of deepest penetration extended 0.8 mm from a glandular basement membrane and had laterai spread of 0.4 mm. All measurements were made with an optical micrometer. One area was suspicious for lymph-vascular space invasion but this could not be confirmed by step sections. Most of the remaining sections contained high grade dysplasia with glandular space involvement. Resection margins were negative for both invasive tumor and intraepithelial neoplasia. Physical ixamination revealed an irregular cervix with a healing biopsy site. The uterus was slightly enlarged. Left parametrial induration was palpable but resolved after antibiotic therapy. Chest radiograph, laboratory studies, and intravenous pyelogram were normal.
219 0090-8258/89$1.JO Copyright 0 1989 by Academic Press, Inc. All rights of reproduction in any form reserved.
220
COLLINS ET AL.
FIG. 1. Photomicrograph of a section from the cone biopsy demonstrating a focus of invasion extending 0.1 mm from the overlying basement membrane (hematoxylin and eosin x 100).
FIG. 2. This left para-aortic lymph node has been extensively in1filtrated by metastatic squamous cell carcinoma (hematoxylin and eosin X 100).
At exploration for planned abdominal hysterectomy, a 10 x IO-cm irregular retroperitoneal nodal mass encasing the left common and internal iliac vessels was found. There were several enlarged para-aortic lymph nodes with one node densely adhered to the aortic wall at the level of the inferior mesenteric artery. There was no palpable parametrial or pelvic sidewall disease. Upper abdominal examination was normal. Frozen section diagnosis from pelvic and para-aortic lymph node biopsies was metastatic squamous cell carcinoma. Hysterectomy was abandoned. Final pathology review confirmed metastatic squamous cell carcinoma in pelvic and para-aortic lymph nodes (Fig. 2). Postoperatively the patient received combined modality therapy with standard whole pelvis irradiation and systemic &-platinum chemotherapy. She developed progressive para-aortic and scalene node disease while under treatment and died 7 months later.
DISCUSSION Most of the definition-related controversies surrounding microinvasive cervical carcinoma have been resolved by changes in clinical staging approved by the Intemational Federation of Gynecology and Obstetrics (FIGO) in 1985 [9]. The new definition for Stage IA cervical cancer incorporates measurement of both depth of invasion from the base of the epithelium and lateral spread, but ignores lymph-vascular space invasion, growth pattern, degree of differentiation, and stromal inflammatory response. While the relative prognostic significance of each of these histologic variables has often been debated, most reviews have demonstrated incremental increases in the risk of lymph node metastasis with increasing depth of invasion or tumor volume [l-S]. Because nodal metastasis in cervical carcinoma is associated with a significant risk of recurrence and reduced survival, es-
221
CASE REPORT
timates of nodal involvement are important in determining optimal therapy [ 10,l I]. The diagnosis of Stage IA cervical carcinoma can be difficult. Extension of high grade epithelial dysplasia into cervical glands is often difficult to distinguish from true invasion. Stromal inflammatory infiltrates may obscure basement membrane detail and mask early invasion. The magnitude of these diagnostic problems is illustrated by Sedlis and colleagues’ review of a Gynecologic Oncology Group study in which 126 of 265 cases were excluded because histologic criteria for microinvasion could not be substantiated by the reviewing pathologists [6]. The cone biopsy specimen from our patient was initially processed in 12 tissue blocks with l-2 sections taken from each block. Step sections were obtained from multiple blocks. The specimen was sectioned a second time after metastatic disease was found at laparotomy. No areas of deeper invasion were seen. Endocervical, ectocervical, and deep resection margins were clear on all slides. Endocervical and endometrial curettings contained no tumor. The diagnosis of early stromal invasion was, therefore, felt to be correct. One other case of extensive nodal metastasis had been reported in a patient with less than 1 mm invasion. In his discussion of van Nagell’s paper [8], Averette described a patient with 0.2 mm invasion and lymph-vascular space involvement who had bulky pelvic node metastases at laparotomy. Following surgical resection of metastatic disease, she was treated with radon seed implant, intracavitary and extended field external beam radiotherapy. This patient remained clinically free of disease 4.5 years later. The management of patients with Stage IA cervical carcinoma should be individualized. Averette and coworkers reported no lymph node metastases and no recurrences in 162 patients with tumors invading less than 1 mm and showing no lymph-vascular space involvement [l]. They recommended that radical hysterectomy be used to treat patients with invasion greater than 1 mm because the risk of nodal metastasis exceeded the surgical risk in this group. Others have suggested that conservative surgical procedures can be safely applied to the majority of patients with invasion up to 3 mm [2-
81. The two cases described demonstrate that any degree of stromal invasion carries some risk of nodal spread. An abdominal approach should be considered for patients treated by extrafascial hysterectomy to allow clinical and/or pathological assessment of regional lymph nodes so that the rare patient with metastatic disease can be identified. Whether more aggressive therapy will influence the outcome for these patients is unknown. REFERENCES 1. Averette, H. E., Nelson, J. A., Jr., Ng, A. B. P., Hoskins, W. J., Boyce, J. G., and Ford, J. H., Jr. Diagnosis and management of microinvasive (Stage IA) carcinoma of the uterine cervix, Cancer 38, 414-425 (1976). 2. Burghardt, E., and Holzer, E. Diagnosis and treatment of microinvasive carcinoma of the cervix uteri, Obstet. Gynecol. 49, 641-653 (1977). 3. Creasman, W. T., Fetter, B. F., Clarke-Pearson, D. L., Kaufmann, L., and Parker, R. T. Management of Stage IA carcinoma of the cervix, Amer. J. Obstet. Gynecol. 153, 164-172 (1985). 4. Leman,M. H., Benson,W. L., Kurman,R. J., and Park, R. C. Microinvasive carcinoma of the cervix, Obstet. Gynecol. 48, 571578 (1976). 5. Lohe, K. J., Burghardt, E., Hillemanns, H. G., Kaufmann, C., Ober, K. G., and Zander, J. Early squamous cell carcinoma of the uterine cervix. II. Clinical results of a cooperative study in the management of 419 patients with early stromal invasion and microcarcinoma, Gynecol. Oncol. 6, 31-50 (1978). 6. Sedlis, A., Sail, S., Tsukada, Y., Park, R., Mangan, C., Shingleton, H., and Blessing, J. A. Microinvasive carcinoma of the uterine cervix: A clinical-pathologic study, Amer. J. Obstet. Gynecol. 133, 64-74 (1979). 7. Simon, N. L., Gore, H., Shingleton, H. M., Soong, S., Orr, J. W., Jr., and Hatch, K. D. Study of superficially invasive carcinoma of the cervix, Obstet. Gynecol. 68, 19-24 (1986). 8. van Nagell, J. R., Jr., Greenwell, N., Powell, D. F., Donaldson, G. S., Hanson, M. B., and Gay, E. C. Microinvasive carcinoma of the cervix, Amer. J. Obstet. Gynecol. 145, 981-991 (1983). 9. Changes in definitions of clinical staging for carcinoma of the cervix and ovary: International Federation of Gynecology and Obstetrics, Amer. .I. Obstet. Gynecol. 156, 263-264 (1987). 10. Buchsbaum, H. J. Extrapelvic lymph node metastases in cervical carcinoma, Amer. J. Obstet. Gynecol. 133, 814-824 (1979). 11. Lagasse, L. D., Creasman, W. T., Shingleton, H. M., Ford, J. H., and Blessing, J. A. Results and complications of operative staging in cervical cancer: Experience of the Gynecologic Oncology Group, Gynecol. Oncol. 9, 90-98 (1980).
ONCOLOGY
34,
219-221 (1989)
CASE REPORT Widespread Lymph Node Metastases in a Patient with Microinvasive Cervical Carcinoma’ HARRY S. COLLINS, MAJ. M.C. U.S.A., THOMAS W. BURKE, MAJ. M.C. U.S.A. ,* JOAN E. WOODWARD, MAJ. M.C. U.S.A., JOHN W. SPURLOCK,CPT. M.C. U.S.A., AND PAUL B. HELLER, COL. M.C. U.S.A. Gynecologic
Oncology
and Pathology
Services,
Walter Reed Army Medical
Center, Washington,
D.C. 20307-5001
Received April 26, 1988
Lymph node metastasis is uncommon in patients with microinvasive squamous cell carcinoma of the cervix and is particularly unusual in tumors with early stromal invasion. We describe a patient with maxhnum stromal invasion of 0.8 mm who had extensive pelvic and para-aortic nodal metastasesdiscovered at laparotomy. Despite combined modality therapy, she died with progressive disease. New clinical staging definitions for Stage IA cervical carcinoma incorporate measurement of both depth of invasion and lateral tumor spread and have resolved many of the descriptive controversies surrounding this entity., Our case illustrates that any degree of stromal invasion carries some risk of nodal metastasis. The management of patients with microinvasive carcinoma should be individualized. An abdominal approach should be considered for patients being treated by extrafascial hysterectomy to allow assessmentof the regional lymph nodes. Whether more aggressive therapy will hrfluence the outcome for the rare patient with lymph node metastasis is unknown. 8 19ag Academic I’rcss, Inc.
Microinvasive squamous cell carcinoma of the cervix is normally characterized by a low incidence of lymph node metastasis and an excellent prognosis [l-8]. Lymph node metastasis has been particularly uncommon in tumors with early stromal invasion [1,3,4,6-81 or small volume [2,5]. This report describes a patient with minimally invasive (
CASE HISTORY A 33-year-old black gravida 4 para 4 was referred to Walter Reed Army Medical Center after a cone biopsy demonstrated microinvasive squamous cell carcinoma of the cervix. Colposcopic evaluation for an abnormal Papanicolaou smear 15 months earlier had shown CIN III with a positive endocervical curettage. She refused recommended cone biopsy and was not seen until 3 months prior to referral. Repeat colposcopic examination with biopsies demonstrated CIN III with dysplastic epithelium present in endocervical curettings. She again delayed diagnostic cone biopsy but was finally persuaded to undergo the procedure. Histologic review of multiple sections and step sections from the cone biopsy specimen confirmed the diagnosis of microinvasive squamous cell carcinoma. Several sites of early stromal invasion were seen in sections from a single tissue block. All but one of these were small buds of invasive tumor extending ~0.2 mm from the basement membrane (Fig. 1). The area of deepest penetration extended 0.8 mm from a glandular basement membrane and had laterai spread of 0.4 mm. All measurements were made with an optical micrometer. One area was suspicious for lymph-vascular space invasion but this could not be confirmed by step sections. Most of the remaining sections contained high grade dysplasia with glandular space involvement. Resection margins were negative for both invasive tumor and intraepithelial neoplasia. Physical ixamination revealed an irregular cervix with a healing biopsy site. The uterus was slightly enlarged. Left parametrial induration was palpable but resolved after antibiotic therapy. Chest radiograph, laboratory studies, and intravenous pyelogram were normal.
219 0090-8258/89$1.JO Copyright 0 1989 by Academic Press, Inc. All rights of reproduction in any form reserved.
220
COLLINS ET AL.
FIG. 1. Photomicrograph of a section from the cone biopsy demonstrating a focus of invasion extending 0.1 mm from the overlying basement membrane (hematoxylin and eosin x 100).
FIG. 2. This left para-aortic lymph node has been extensively in1filtrated by metastatic squamous cell carcinoma (hematoxylin and eosin X 100).
At exploration for planned abdominal hysterectomy, a 10 x IO-cm irregular retroperitoneal nodal mass encasing the left common and internal iliac vessels was found. There were several enlarged para-aortic lymph nodes with one node densely adhered to the aortic wall at the level of the inferior mesenteric artery. There was no palpable parametrial or pelvic sidewall disease. Upper abdominal examination was normal. Frozen section diagnosis from pelvic and para-aortic lymph node biopsies was metastatic squamous cell carcinoma. Hysterectomy was abandoned. Final pathology review confirmed metastatic squamous cell carcinoma in pelvic and para-aortic lymph nodes (Fig. 2). Postoperatively the patient received combined modality therapy with standard whole pelvis irradiation and systemic &-platinum chemotherapy. She developed progressive para-aortic and scalene node disease while under treatment and died 7 months later.
DISCUSSION Most of the definition-related controversies surrounding microinvasive cervical carcinoma have been resolved by changes in clinical staging approved by the Intemational Federation of Gynecology and Obstetrics (FIGO) in 1985 [9]. The new definition for Stage IA cervical cancer incorporates measurement of both depth of invasion from the base of the epithelium and lateral spread, but ignores lymph-vascular space invasion, growth pattern, degree of differentiation, and stromal inflammatory response. While the relative prognostic significance of each of these histologic variables has often been debated, most reviews have demonstrated incremental increases in the risk of lymph node metastasis with increasing depth of invasion or tumor volume [l-S]. Because nodal metastasis in cervical carcinoma is associated with a significant risk of recurrence and reduced survival, es-
221
CASE REPORT
timates of nodal involvement are important in determining optimal therapy [ 10,l I]. The diagnosis of Stage IA cervical carcinoma can be difficult. Extension of high grade epithelial dysplasia into cervical glands is often difficult to distinguish from true invasion. Stromal inflammatory infiltrates may obscure basement membrane detail and mask early invasion. The magnitude of these diagnostic problems is illustrated by Sedlis and colleagues’ review of a Gynecologic Oncology Group study in which 126 of 265 cases were excluded because histologic criteria for microinvasion could not be substantiated by the reviewing pathologists [6]. The cone biopsy specimen from our patient was initially processed in 12 tissue blocks with l-2 sections taken from each block. Step sections were obtained from multiple blocks. The specimen was sectioned a second time after metastatic disease was found at laparotomy. No areas of deeper invasion were seen. Endocervical, ectocervical, and deep resection margins were clear on all slides. Endocervical and endometrial curettings contained no tumor. The diagnosis of early stromal invasion was, therefore, felt to be correct. One other case of extensive nodal metastasis had been reported in a patient with less than 1 mm invasion. In his discussion of van Nagell’s paper [8], Averette described a patient with 0.2 mm invasion and lymph-vascular space involvement who had bulky pelvic node metastases at laparotomy. Following surgical resection of metastatic disease, she was treated with radon seed implant, intracavitary and extended field external beam radiotherapy. This patient remained clinically free of disease 4.5 years later. The management of patients with Stage IA cervical carcinoma should be individualized. Averette and coworkers reported no lymph node metastases and no recurrences in 162 patients with tumors invading less than 1 mm and showing no lymph-vascular space involvement [l]. They recommended that radical hysterectomy be used to treat patients with invasion greater than 1 mm because the risk of nodal metastasis exceeded the surgical risk in this group. Others have suggested that conservative surgical procedures can be safely applied to the majority of patients with invasion up to 3 mm [2-
81. The two cases described demonstrate that any degree of stromal invasion carries some risk of nodal spread. An abdominal approach should be considered for patients treated by extrafascial hysterectomy to allow clinical and/or pathological assessment of regional lymph nodes so that the rare patient with metastatic disease can be identified. Whether more aggressive therapy will influence the outcome for these patients is unknown. REFERENCES 1. Averette, H. E., Nelson, J. A., Jr., Ng, A. B. P., Hoskins, W. J., Boyce, J. G., and Ford, J. H., Jr. Diagnosis and management of microinvasive (Stage IA) carcinoma of the uterine cervix, Cancer 38, 414-425 (1976). 2. Burghardt, E., and Holzer, E. Diagnosis and treatment of microinvasive carcinoma of the cervix uteri, Obstet. Gynecol. 49, 641-653 (1977). 3. Creasman, W. T., Fetter, B. F., Clarke-Pearson, D. L., Kaufmann, L., and Parker, R. T. Management of Stage IA carcinoma of the cervix, Amer. J. Obstet. Gynecol. 153, 164-172 (1985). 4. Leman,M. H., Benson,W. L., Kurman,R. J., and Park, R. C. Microinvasive carcinoma of the cervix, Obstet. Gynecol. 48, 571578 (1976). 5. Lohe, K. J., Burghardt, E., Hillemanns, H. G., Kaufmann, C., Ober, K. G., and Zander, J. Early squamous cell carcinoma of the uterine cervix. II. Clinical results of a cooperative study in the management of 419 patients with early stromal invasion and microcarcinoma, Gynecol. Oncol. 6, 31-50 (1978). 6. Sedlis, A., Sail, S., Tsukada, Y., Park, R., Mangan, C., Shingleton, H., and Blessing, J. A. Microinvasive carcinoma of the uterine cervix: A clinical-pathologic study, Amer. J. Obstet. Gynecol. 133, 64-74 (1979). 7. Simon, N. L., Gore, H., Shingleton, H. M., Soong, S., Orr, J. W., Jr., and Hatch, K. D. Study of superficially invasive carcinoma of the cervix, Obstet. Gynecol. 68, 19-24 (1986). 8. van Nagell, J. R., Jr., Greenwell, N., Powell, D. F., Donaldson, G. S., Hanson, M. B., and Gay, E. C. Microinvasive carcinoma of the cervix, Amer. J. Obstet. Gynecol. 145, 981-991 (1983). 9. Changes in definitions of clinical staging for carcinoma of the cervix and ovary: International Federation of Gynecology and Obstetrics, Amer. .I. Obstet. Gynecol. 156, 263-264 (1987). 10. Buchsbaum, H. J. Extrapelvic lymph node metastases in cervical carcinoma, Amer. J. Obstet. Gynecol. 133, 814-824 (1979). 11. Lagasse, L. D., Creasman, W. T., Shingleton, H. M., Ford, J. H., and Blessing, J. A. Results and complications of operative staging in cervical cancer: Experience of the Gynecologic Oncology Group, Gynecol. Oncol. 9, 90-98 (1980).