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Lymph node metastasis in cancer of the cervix: A preliminary report
Bloxam and Bullen
7.
8.
9. 10. II.
olism of glucose and lactate in the human placenta studied by a perfusion system in vitro. Placenta 1981 (suppl)2: 12938. Brandes ]M, Tavoloni N, Potter B], Sarkozi L, Shepard MD, Berk PD. A new recycling technique for human placental cotyledon perfusion: application to studies of the fetomaternal transfer of glucose, inulin, and antipyrine. AM] OBSTET GY:-;ECOL 1983;146:800-6. Hauguel S, Challier ]C, Cedard L, Olive G. Metabolism of the human placenta perfused in vitro: glucose transfer and utilization, 0, consumption, lactate and ammonia production. Pediatr Res 1983; 17:729-32. Bloxam DL, Bobinski M. Energy metabolism and glycolysis in the human placenta during ischaemia and in normal labour. Placenta 1984;5:381-94. Schneider H, Panigel M, Dancis.J. Transfer across the perfused human placenta of antipyrine, sodium, and leucine. A:vtJ OBSTET GYNECOL 1972;114:822-8. Waalkes TP, Udenfriend S. A ftuorometric method for
August 1986 Am J Obstet Gynecol
12. 13. 14. 15.
16.
the estimation of tyrosine in plasma and tissues. ] Lab Clin Med 1957;50:733-6. McCaman MW, Robins E. Fluorimetric method for the determination of phenylalanine in serum. J Lab Clin Med 1962;59:885-90. Bloxam DL, Warren WHo Error in the determination of tryptophan by the method of Denckla and Dewey. A revised procedure. Anal Biochem 1974;60:621-5. States B, Segal S. Quantitation of cyst(e)ine in human fibroblasts and separation of cysteinesulfinic acid, cysteic acid and taurine. Clin Chim Acta 1973;43:49-53. Williamson BH. L-Alanine. Determination with alanine dehydrogenase. In: Bergmeyer HU, ed. Methods of enzymatic analysis. 2d English ed. London: Academic Press, 1974, vol 4:1679-82. Tiller ]M, Bloxam DL. An enzymatic ftuorometric assay for L-lysine in plasma and tissue. Anal Biochem 1983; 131 :426-9.
Lymph node metastasis in cancer of the cervix: A preliminary report Alexander C. W. To, Ph.D., Hazel Gore, M.B., B.S., Hugh M. Shingleton, M.D., James A. Wilkerson, M.D., Seng Jaw Soong, Ph.D., and Kenneth D. Hatch, M.D. Birmingham, Alabama Accurate assessment of lymph node metastasis in cervical cancer is imperative to treatment plan. A histologic sampling method is suggested in which surgically excised lymph nodes are dissected at multiple levels before paraffin embedding. This approach proves to be a more sensitive procedure than the current bisection method in detecting metastasis. (AM J OSSTET GYNECOL 1986;155:388-9.)
Key words: Lymph node metastasis, cervical cancer, pathology technique In cancer of the cervix, tumor metastasis to the lymph nodes adversely affects patient survival. The 5-year survival rate for Stage IB lesions is 90% if the lymph nodes are negative, whereas it ranges from 40% to 80% if they are positive. I The number of positive nodes, the unilateral or bilateral location of the positive nodes and the involvement of pelvic, para-aortic, or supraclavicular nodes all are related to the subsequent prognosis. Accurate assessment of the lymph node status is imperative in determination of the extent of disease and the type and extent of treatment. The diagnosis of lymph node metastasis is based on
From the Departments of Obstetrics and Gynecology and Pathology and the Comprehensive Cancer Center, University of Alabama at Birmingham. Received for publication October 25, 1985; revised March 3, 1986; accepted March 19, 1986. Reprint requests: A. C. W. To, Ph.D., Department of Obstetrics and Gynecology, UAB Medical Center, University Station, Birmingham, AL 35294.
388
pathologic examination of the surgically excised lymph nodes. The present histologic method of sampling the nodes usually provides only a bisection of each node for microscopic examination (Fig. 1). Ahrens and Tschoke reassessed lymph nodes by serial sectioning of the node-bearing paraffin blocks and found more than 100% diagnostic error (false negative) compared with the results of the original pathologic examination. Wilkinson and Hause" demonstrated that further sampling of the nodes at different levels is associated with a significant increase in the incidence of positive nodes. Given the facts that presence of positive nodes is determinative to treatment plan and patient survival and that further node sampling can increase the incidence of positive nodes, there is a great need to enhance the diagnostic accuracy of the current lymph node examination. A technique that is aimed at such an improvement must be routinely applicable in terms of labor intensiveness and cost effectiveness. Past studies of lymph node investigation involved se-
Lymph node metastasis in cervical cancer
Volume 155 Number 2
rial sections of the nodal blocks. This experimental approach demonstrated the presence of undetected metastasis in a precise, quantitative manner but poses two problems in routine practice. First, the number of sections to be screened per patient is prohibitively high. Second, for examination of various levels throughout a nodal block, the tissue ribbons sectioned between the levels would have to be mounted in order to keep a record of the tissue. This, per node, can number more than a hundred unnecessary slides.
t
8 +
NODAL BISECTION
C) C) EMBEDDING
389
.,. NODAL MUL TI-DlSSECTlm~
+ OOC:::;)c::::Jc::::Jc::::.Jc:=?Q EMBEDDING
+
Method and results
One potential approach to improve the sampling efficiency would be to dissect the node at various levels before paraffin embedding.' This enables different levels of the nodes to be cut, mounted, and examined on one slide (Fig. 1). To evaluate the effectiveness of this approach, we carried out a pilot retrospective study on paraffin blocks of surgically excised lymph nodes from 35 patients with Stage IB lesions. All surgical excisions were carried out by senior gynecologic oncologists and past fellows to minimize variation in extent and quality of the nodal excision. Twenty of these patients had subsequent recurrence of disease and the remaining 15 were free of disease 5 years after the initial diagnosis. All of the original lymph node specimens were examined but different surgical pathologists carried out the examination. Thus all of the original slides stained with hematoxylin and eosin were reviewed by a single surgical pathologist to confirm the initial examination. The blocks were then dewaxed, and the nodes were redissected at multilevels, reembedded, sectioned, mounted, and reexamined microscopically (Fig. 1). The results indicated that three of the 20 patients with recurrence were each found to have one positive node, whereas none of the 15 disease-free patients was found to have a positive node. This pilot study showed that three of 35 patients (9%) reported to have negative nodes actually had positive nodes, and three of 20 patients (15%) with subsequent
MICPOSCOPE SLIDE
+ HISTOLOGICAL
S[CTI()~:
MICPOSCOPE SLIDE
+ HISTOLOGICAL SECTION
Fig. 1. Conventional lymph node bisection versus multilevel dissection.
disease recurrence had positive nodes. The false negative rate in either case is significantly high enough to warrant a larger series of study to confirm clinical utility before romine application. REFERENCES 1. Shingleton HM, Orr JW Jr. Cancer of the cervix: diagnosis and treatment. New York: Churchill Livingstone, 1983. 2. Ahrens CA, Tschoke S. Lymphknotenbefunde nach Wertheim-Meigscher Operation. Geburtshilfe Frauenheilkd 1961;21:219-24. 3. Wilkinson EJ, Hause L. Probability in lymph node sectioning. Cancer 1974;33:1269-74.
7.
8.
9. 10. II.
olism of glucose and lactate in the human placenta studied by a perfusion system in vitro. Placenta 1981 (suppl)2: 12938. Brandes ]M, Tavoloni N, Potter B], Sarkozi L, Shepard MD, Berk PD. A new recycling technique for human placental cotyledon perfusion: application to studies of the fetomaternal transfer of glucose, inulin, and antipyrine. AM] OBSTET GY:-;ECOL 1983;146:800-6. Hauguel S, Challier ]C, Cedard L, Olive G. Metabolism of the human placenta perfused in vitro: glucose transfer and utilization, 0, consumption, lactate and ammonia production. Pediatr Res 1983; 17:729-32. Bloxam DL, Bobinski M. Energy metabolism and glycolysis in the human placenta during ischaemia and in normal labour. Placenta 1984;5:381-94. Schneider H, Panigel M, Dancis.J. Transfer across the perfused human placenta of antipyrine, sodium, and leucine. A:vtJ OBSTET GYNECOL 1972;114:822-8. Waalkes TP, Udenfriend S. A ftuorometric method for
August 1986 Am J Obstet Gynecol
12. 13. 14. 15.
16.
the estimation of tyrosine in plasma and tissues. ] Lab Clin Med 1957;50:733-6. McCaman MW, Robins E. Fluorimetric method for the determination of phenylalanine in serum. J Lab Clin Med 1962;59:885-90. Bloxam DL, Warren WHo Error in the determination of tryptophan by the method of Denckla and Dewey. A revised procedure. Anal Biochem 1974;60:621-5. States B, Segal S. Quantitation of cyst(e)ine in human fibroblasts and separation of cysteinesulfinic acid, cysteic acid and taurine. Clin Chim Acta 1973;43:49-53. Williamson BH. L-Alanine. Determination with alanine dehydrogenase. In: Bergmeyer HU, ed. Methods of enzymatic analysis. 2d English ed. London: Academic Press, 1974, vol 4:1679-82. Tiller ]M, Bloxam DL. An enzymatic ftuorometric assay for L-lysine in plasma and tissue. Anal Biochem 1983; 131 :426-9.
Lymph node metastasis in cancer of the cervix: A preliminary report Alexander C. W. To, Ph.D., Hazel Gore, M.B., B.S., Hugh M. Shingleton, M.D., James A. Wilkerson, M.D., Seng Jaw Soong, Ph.D., and Kenneth D. Hatch, M.D. Birmingham, Alabama Accurate assessment of lymph node metastasis in cervical cancer is imperative to treatment plan. A histologic sampling method is suggested in which surgically excised lymph nodes are dissected at multiple levels before paraffin embedding. This approach proves to be a more sensitive procedure than the current bisection method in detecting metastasis. (AM J OSSTET GYNECOL 1986;155:388-9.)
Key words: Lymph node metastasis, cervical cancer, pathology technique In cancer of the cervix, tumor metastasis to the lymph nodes adversely affects patient survival. The 5-year survival rate for Stage IB lesions is 90% if the lymph nodes are negative, whereas it ranges from 40% to 80% if they are positive. I The number of positive nodes, the unilateral or bilateral location of the positive nodes and the involvement of pelvic, para-aortic, or supraclavicular nodes all are related to the subsequent prognosis. Accurate assessment of the lymph node status is imperative in determination of the extent of disease and the type and extent of treatment. The diagnosis of lymph node metastasis is based on
From the Departments of Obstetrics and Gynecology and Pathology and the Comprehensive Cancer Center, University of Alabama at Birmingham. Received for publication October 25, 1985; revised March 3, 1986; accepted March 19, 1986. Reprint requests: A. C. W. To, Ph.D., Department of Obstetrics and Gynecology, UAB Medical Center, University Station, Birmingham, AL 35294.
388
pathologic examination of the surgically excised lymph nodes. The present histologic method of sampling the nodes usually provides only a bisection of each node for microscopic examination (Fig. 1). Ahrens and Tschoke reassessed lymph nodes by serial sectioning of the node-bearing paraffin blocks and found more than 100% diagnostic error (false negative) compared with the results of the original pathologic examination. Wilkinson and Hause" demonstrated that further sampling of the nodes at different levels is associated with a significant increase in the incidence of positive nodes. Given the facts that presence of positive nodes is determinative to treatment plan and patient survival and that further node sampling can increase the incidence of positive nodes, there is a great need to enhance the diagnostic accuracy of the current lymph node examination. A technique that is aimed at such an improvement must be routinely applicable in terms of labor intensiveness and cost effectiveness. Past studies of lymph node investigation involved se-
Lymph node metastasis in cervical cancer
Volume 155 Number 2
rial sections of the nodal blocks. This experimental approach demonstrated the presence of undetected metastasis in a precise, quantitative manner but poses two problems in routine practice. First, the number of sections to be screened per patient is prohibitively high. Second, for examination of various levels throughout a nodal block, the tissue ribbons sectioned between the levels would have to be mounted in order to keep a record of the tissue. This, per node, can number more than a hundred unnecessary slides.
t
8 +
NODAL BISECTION
C) C) EMBEDDING
389
.,. NODAL MUL TI-DlSSECTlm~
+ OOC:::;)c::::Jc::::Jc::::.Jc:=?Q EMBEDDING
+
Method and results
One potential approach to improve the sampling efficiency would be to dissect the node at various levels before paraffin embedding.' This enables different levels of the nodes to be cut, mounted, and examined on one slide (Fig. 1). To evaluate the effectiveness of this approach, we carried out a pilot retrospective study on paraffin blocks of surgically excised lymph nodes from 35 patients with Stage IB lesions. All surgical excisions were carried out by senior gynecologic oncologists and past fellows to minimize variation in extent and quality of the nodal excision. Twenty of these patients had subsequent recurrence of disease and the remaining 15 were free of disease 5 years after the initial diagnosis. All of the original lymph node specimens were examined but different surgical pathologists carried out the examination. Thus all of the original slides stained with hematoxylin and eosin were reviewed by a single surgical pathologist to confirm the initial examination. The blocks were then dewaxed, and the nodes were redissected at multilevels, reembedded, sectioned, mounted, and reexamined microscopically (Fig. 1). The results indicated that three of the 20 patients with recurrence were each found to have one positive node, whereas none of the 15 disease-free patients was found to have a positive node. This pilot study showed that three of 35 patients (9%) reported to have negative nodes actually had positive nodes, and three of 20 patients (15%) with subsequent
MICPOSCOPE SLIDE
+ HISTOLOGICAL
S[CTI()~:
MICPOSCOPE SLIDE
+ HISTOLOGICAL SECTION
Fig. 1. Conventional lymph node bisection versus multilevel dissection.
disease recurrence had positive nodes. The false negative rate in either case is significantly high enough to warrant a larger series of study to confirm clinical utility before romine application. REFERENCES 1. Shingleton HM, Orr JW Jr. Cancer of the cervix: diagnosis and treatment. New York: Churchill Livingstone, 1983. 2. Ahrens CA, Tschoke S. Lymphknotenbefunde nach Wertheim-Meigscher Operation. Geburtshilfe Frauenheilkd 1961;21:219-24. 3. Wilkinson EJ, Hause L. Probability in lymph node sectioning. Cancer 1974;33:1269-74.