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Lymph node metastasis in FIGO stage IA1 cervical cancer?
790
Letters to the Editor
Cooperative Oncology Group registry data and not a review paper, we felt that our discussion should be concise and focused on commenting on the presented data in relation to some of the published works in the field and avoid citing all of the relevant reports in the literature. Finally, although we do agree that designing and carrying out clinical studies on MOC would indeed be quite difficult due to its low incidence rate, it appears to be the only way to address the issue of therapeutic management of these cases. Given the continuously growing number of patients being diagnosed as having ovarian cancer as a result of the general prolongation of life expectancy, a nearly 11–20% incidence of MOC of all stages does not render such a study unrealistic. A potential answer to this problem may be the collaboration of different Oncology Groups so that implementation of largescale trials would be possible. References [1] Omura GA. Re: Mucinous ovarian cancer. Gynecol Oncol; in press. [2] Pectasides D, Fountzilas G, Aravantinos G, et al. Advanced stage mucinous epithelial ovarian cancer: the Hellenic Cooperative Oncology Group experience. Gynecol Oncol 2005;97:436 – 41. [3] Omura GA, Bundy BN, Berek JS, et al. Randomized trial of cyclophosphamide plus cisplatin with or without doxorubicin in ovarian carcinoma: a Gynecologic Oncology Group Study. J Clin Oncol 1989;7:457 – 65.
Dimitrios Pectasides 4 Dimitrios Farmakis Second Department of Internal Medicine-Propaedeutic, Oncology Section, Attikon University General Hospital Home Address: Gravias 5B, Aghia Paraskevi, 153 42 Athens, Greece E-mail addresses: [email protected] (D. Pectasides), [email protected] (D. Farmakis). 4Corresponding author. Fax: +3210 600 8610. 1 July 2005 doi:10.1016/j.ygyno.2005.07.022
Lymph node metastasis in FIGO stage IA1 cervical cancer?B To the Editor: We read with interest the report by Argenta et al. [1] of widespread lymph node metastases in a case of FIGO stage IA1 microinvasive squamous cell carcinoma of the cervix. We question the accuracy of the histological findings described by the authors as well as its derived treatment recommendations. Invasion of cervical squamous cell carcinoma begins from the basal layer of a field of cervical intraepithelial neoplasia B An evaluation of Argenta PA, Kubicek GJ, Dusenberry KE, Judson PL, Downs LS, Carson LF, et al. Widespread lymph node metastases in a young woman with FIGO stage IA1 squamous cervical cancer. Gynecol Oncol 2005;97:659–61.
(CIN) on the ectocervix, in the cervical canal, or in a cervical gland [2]. Approximately 12% of microinvasive squamous cell carcinomas of the cervix have more than one invasive focus when they first invade the cervical stroma [3]. Multicentricity with early invasive foci at numerous sites can occur, but invasion arises from a single field of CIN [4]. Argenta et al. [1] described a single focus of invasive squamous cell carcinoma with a maximum depth of invasion of 1 mm within associated dysplasia in a cone biopsy. The cone was processed by 12 serial sections. All resection margins were reported negative with at least 5 mm to the nearest malignancy or dysplasia. However, subsequent hysterectomy revealed a further focus of invasive squamous cell cancer measuring again V1 mm in total size and this was interpreted as multifocal stage IA1 disease based on the negative margins of the cone specimen. We disagree with the interpretation of two separate invasive squamous cell carcinoma foci disassociated from each other by regular cervical tissue by Argenta et al. [1]. Supposing both microinvasive squamous cell carcinoma foci originated from a single field of CIN, the true extent and stage of disease was truly underestimated. This might be due to the limited number of bserialQ sections (12 cuts) of the cone specimen. Alternatively, if resection margins of the cone biopsy described by Argenta et al. [1] were free of CIN, the invasive focus found in the hysterectomy specimen could represent lymphatic spread within the cervix explaining increased risk of lymph node spread or recurrence associated with vascular space involvement [2,5]. Depth and width are relevant to the prognosis of microinvasive cervical cancers and the 1995 International Federation of Gynecology and Obstetrics (FIGO) criteria stipulate measurement of these lesions in two dimensions. It is necessary to distinguish different growth patterns of microinvasive squamous cell carcinoma to precisely measure lateral tumor extent [4]. Different patterns of multiple invasive foci can be either horizontally measured in a single step-serial section or the width of the entire lesion has to be measured by calculation of distances between all involved step-serial sections. Lesions with a depth of invasion V1 cm and no lymphatic–vascular space involvement carry a risk of invasive recurrence of b0.5% [5]. These patients are ideal candidates for treatment by conization only. Radiological evaluation of the pelvic and paraaortic lymph nodes in these patients is neither necessary nor justified. We base our findings [2–5] on unequivocally precise histological processing of cone specimens over many decades. A medially bisected cone is embedded and then serially sectioned at intervals of 200–300 lm apart until the endocervical canal has disappeared [2]. This technique yields an average of 60–80 sections per cone for accurate histologic diagnosis. The status of cone margins and extent of microinvasive lesions should not be based on evaluation of single sections. Precise histological measurements by step-serial sections are a precondition for staging of cervical microinvasive squamous cell carcinoma before elementary findings in the pursuit of individualized conservative treatment are challenged.
Letters to the Editor
In summary, we believe that the patient reported by Argenta et al. [1] most likely had stage IA2 or IB1 cervical cancer that was not appreciated in the initial pathology. Conservative treatment of early cervical cancer requires extensive evaluation of conization specimens to rule out more advanced disease. References [1] Argenta PA, Kubicek GJ, Dusenberry KE, Judson PL, Downs LS, Carson LF, et al. Widespread lymph node metastases in a young woman with FIGO stage IA1 squamous cervical cancer. Gynecol Oncol 2005;97:659 – 61. [2] Burghardt E, Pickel H, Girardi F. Colposcopy, Cervical Pathology. Textbook and Atlas, 3rd ed. New York7 Thieme, 1998. [3] Reich O, Pickel H, Tamussino K, Winter R. Microinvasive carcinoma of the cervix: site of first focus of invasion. Obstet Gynecol 2001;97:890 – 2. [4] Reich O, Pickel H. Multifocal stromal invasion in microinvasive squamous cell carcionoma of the cervix: how to measure and stage these lesions. Int J Gynecol Pathol 2002;21:416 – 7. [5] Burghardt E, Girardi F, Lahousen M, Pickel H, Tamussino K. Microinvasive carcinoma of the uterine cervix (International Federation of Gynecology and Obstetrics Stage IA). Cancer 1991;67:1037 – 45.
Arnim A. Bader 4 Karl F. Tamussino Olaf Reich Raimund Winter Department of Obstetrics and Gynecology, Medical University of Graz, Auenbruggerplatz 14, A-8036 Graz, Austria E-mail address: [email protected]. 4Corresponding author. Fax: +43 316 385 3061. 9 June 2005
791
information about the three dimensional configuration of the tumor. Weighing against more aggressive sectioning however are: at least a doubling in technical costs, increased potential for artifact abnormalities and interpretive errors, and a paucity of data regarding the prognostic significance of occult microscopic extension. Dr. Reich and colleagues have published extensively on the subject of architectural pathology and have concluded that their results suggest b. . .that multicentricity with early invasive foci at numerous sites can occurQ [3]. Furthermore, current staging systems were designed without the benefit of bunequivocally precise histological processing,Q and the additional information gained from more aggressive sectioning may not have the same prognostic implication as results obtained from standard processing. Drs. Trattner, Reich, and Winter, using semiautomatic image analysis on early stage cervical cancers, have previously observed btumor volume does not seem to confer additional prognostic information if histopathological stage and lymph node status are knownQ [4]. While we cannot entirely exclude the possibility of occult extension, we feel that the weight of evidence supports our assertion that this case represents multi-focal stage IA1 disease. We agree with Dr. Bader and colleagues that extensive sectioning of these specimens is indicated, however, we remain unconvinced that that standard sectioning is inadequate. Rather, we assert that there is likely biologic variability which must be considered when counseling a patient considering conservative management of cancer. Sincerely, Peter A. Argenta MD
doi:10.1016/j.ygyno.2005.07.105
References To the editor: We appreciate the interest and thoughtful remarks of Dr. Bader and colleagues [1] regarding our manuscript bWidespread lymph node metastases in a young woman with FIGO stage IA1 cervical cancerQ [2]. With regard to their concerns about the adequacy of the sectioning we employed, I would first make clear that our standard procedure acquires 3 levels of each of 12 cutsections, thus generating 36 tissue specimens. In retrospect, this could have been made more clear in the manuscript, which we regret. Despite this, our total remains significantly below their recommendation of 60–80 slides per section and begs the question: would additional sectioning have revealed the tumor to be a contiguous stellate mass, and subsequently mandate upstaging? Though the question is not relevant to the management of the patient presented by virtue of her metastatic disease, it is germane to the counseling of patients considering conservative therapy for micro-invasive cervical cancer. Serial sections at 200 lm intervals would, no doubt, give additional
[1] Bader AA, Tamussino KF, Reich O, Winter R. Lymph node metastasis in FIGO stage IA1 cervical cancer? Gynecol Oncol 2005; in press. [2] Argenta PA, Kubicek GJ, Dusenberry KE, Judson PL, Downs Jr LS, Carson LF, et al. Widespread lymph node metastases in a young HIVnegative woman with FIGO stage IA1 squamous cervical cancer. Gynecol Oncol 2005;97:659 – 61. [3] Reich O, Pickel H, Tamussino K, Winter R. Microinvasive carcinoma of the cervix: site of first focus of invasion. Obstet Gynecol 2001;97:890 – 2. [4] Trattner M, Graf AH, Lax S, Forstner R, Dandachi N, Haas J, et al. Prognostic factors in surgically treated stage ib–iib cervical carcinomas with special emphasis on the importance of tumor volume. Gynecol Oncol 2001 (Jul);82(1):11 – 6.
Peter Alexander Argenta Department of Obstetrics and Gynecology, University of Minnesota, 420 Delaware St. SE, MMC 395, Minneapolis, MN 55455, USA E-mail address: [email protected]. 22 June 2005 doi:10.1016/j.ygyno.2005.07.028
Letters to the Editor
Cooperative Oncology Group registry data and not a review paper, we felt that our discussion should be concise and focused on commenting on the presented data in relation to some of the published works in the field and avoid citing all of the relevant reports in the literature. Finally, although we do agree that designing and carrying out clinical studies on MOC would indeed be quite difficult due to its low incidence rate, it appears to be the only way to address the issue of therapeutic management of these cases. Given the continuously growing number of patients being diagnosed as having ovarian cancer as a result of the general prolongation of life expectancy, a nearly 11–20% incidence of MOC of all stages does not render such a study unrealistic. A potential answer to this problem may be the collaboration of different Oncology Groups so that implementation of largescale trials would be possible. References [1] Omura GA. Re: Mucinous ovarian cancer. Gynecol Oncol; in press. [2] Pectasides D, Fountzilas G, Aravantinos G, et al. Advanced stage mucinous epithelial ovarian cancer: the Hellenic Cooperative Oncology Group experience. Gynecol Oncol 2005;97:436 – 41. [3] Omura GA, Bundy BN, Berek JS, et al. Randomized trial of cyclophosphamide plus cisplatin with or without doxorubicin in ovarian carcinoma: a Gynecologic Oncology Group Study. J Clin Oncol 1989;7:457 – 65.
Dimitrios Pectasides 4 Dimitrios Farmakis Second Department of Internal Medicine-Propaedeutic, Oncology Section, Attikon University General Hospital Home Address: Gravias 5B, Aghia Paraskevi, 153 42 Athens, Greece E-mail addresses: [email protected] (D. Pectasides), [email protected] (D. Farmakis). 4Corresponding author. Fax: +3210 600 8610. 1 July 2005 doi:10.1016/j.ygyno.2005.07.022
Lymph node metastasis in FIGO stage IA1 cervical cancer?B To the Editor: We read with interest the report by Argenta et al. [1] of widespread lymph node metastases in a case of FIGO stage IA1 microinvasive squamous cell carcinoma of the cervix. We question the accuracy of the histological findings described by the authors as well as its derived treatment recommendations. Invasion of cervical squamous cell carcinoma begins from the basal layer of a field of cervical intraepithelial neoplasia B An evaluation of Argenta PA, Kubicek GJ, Dusenberry KE, Judson PL, Downs LS, Carson LF, et al. Widespread lymph node metastases in a young woman with FIGO stage IA1 squamous cervical cancer. Gynecol Oncol 2005;97:659–61.
(CIN) on the ectocervix, in the cervical canal, or in a cervical gland [2]. Approximately 12% of microinvasive squamous cell carcinomas of the cervix have more than one invasive focus when they first invade the cervical stroma [3]. Multicentricity with early invasive foci at numerous sites can occur, but invasion arises from a single field of CIN [4]. Argenta et al. [1] described a single focus of invasive squamous cell carcinoma with a maximum depth of invasion of 1 mm within associated dysplasia in a cone biopsy. The cone was processed by 12 serial sections. All resection margins were reported negative with at least 5 mm to the nearest malignancy or dysplasia. However, subsequent hysterectomy revealed a further focus of invasive squamous cell cancer measuring again V1 mm in total size and this was interpreted as multifocal stage IA1 disease based on the negative margins of the cone specimen. We disagree with the interpretation of two separate invasive squamous cell carcinoma foci disassociated from each other by regular cervical tissue by Argenta et al. [1]. Supposing both microinvasive squamous cell carcinoma foci originated from a single field of CIN, the true extent and stage of disease was truly underestimated. This might be due to the limited number of bserialQ sections (12 cuts) of the cone specimen. Alternatively, if resection margins of the cone biopsy described by Argenta et al. [1] were free of CIN, the invasive focus found in the hysterectomy specimen could represent lymphatic spread within the cervix explaining increased risk of lymph node spread or recurrence associated with vascular space involvement [2,5]. Depth and width are relevant to the prognosis of microinvasive cervical cancers and the 1995 International Federation of Gynecology and Obstetrics (FIGO) criteria stipulate measurement of these lesions in two dimensions. It is necessary to distinguish different growth patterns of microinvasive squamous cell carcinoma to precisely measure lateral tumor extent [4]. Different patterns of multiple invasive foci can be either horizontally measured in a single step-serial section or the width of the entire lesion has to be measured by calculation of distances between all involved step-serial sections. Lesions with a depth of invasion V1 cm and no lymphatic–vascular space involvement carry a risk of invasive recurrence of b0.5% [5]. These patients are ideal candidates for treatment by conization only. Radiological evaluation of the pelvic and paraaortic lymph nodes in these patients is neither necessary nor justified. We base our findings [2–5] on unequivocally precise histological processing of cone specimens over many decades. A medially bisected cone is embedded and then serially sectioned at intervals of 200–300 lm apart until the endocervical canal has disappeared [2]. This technique yields an average of 60–80 sections per cone for accurate histologic diagnosis. The status of cone margins and extent of microinvasive lesions should not be based on evaluation of single sections. Precise histological measurements by step-serial sections are a precondition for staging of cervical microinvasive squamous cell carcinoma before elementary findings in the pursuit of individualized conservative treatment are challenged.
Letters to the Editor
In summary, we believe that the patient reported by Argenta et al. [1] most likely had stage IA2 or IB1 cervical cancer that was not appreciated in the initial pathology. Conservative treatment of early cervical cancer requires extensive evaluation of conization specimens to rule out more advanced disease. References [1] Argenta PA, Kubicek GJ, Dusenberry KE, Judson PL, Downs LS, Carson LF, et al. Widespread lymph node metastases in a young woman with FIGO stage IA1 squamous cervical cancer. Gynecol Oncol 2005;97:659 – 61. [2] Burghardt E, Pickel H, Girardi F. Colposcopy, Cervical Pathology. Textbook and Atlas, 3rd ed. New York7 Thieme, 1998. [3] Reich O, Pickel H, Tamussino K, Winter R. Microinvasive carcinoma of the cervix: site of first focus of invasion. Obstet Gynecol 2001;97:890 – 2. [4] Reich O, Pickel H. Multifocal stromal invasion in microinvasive squamous cell carcionoma of the cervix: how to measure and stage these lesions. Int J Gynecol Pathol 2002;21:416 – 7. [5] Burghardt E, Girardi F, Lahousen M, Pickel H, Tamussino K. Microinvasive carcinoma of the uterine cervix (International Federation of Gynecology and Obstetrics Stage IA). Cancer 1991;67:1037 – 45.
Arnim A. Bader 4 Karl F. Tamussino Olaf Reich Raimund Winter Department of Obstetrics and Gynecology, Medical University of Graz, Auenbruggerplatz 14, A-8036 Graz, Austria E-mail address: [email protected]. 4Corresponding author. Fax: +43 316 385 3061. 9 June 2005
791
information about the three dimensional configuration of the tumor. Weighing against more aggressive sectioning however are: at least a doubling in technical costs, increased potential for artifact abnormalities and interpretive errors, and a paucity of data regarding the prognostic significance of occult microscopic extension. Dr. Reich and colleagues have published extensively on the subject of architectural pathology and have concluded that their results suggest b. . .that multicentricity with early invasive foci at numerous sites can occurQ [3]. Furthermore, current staging systems were designed without the benefit of bunequivocally precise histological processing,Q and the additional information gained from more aggressive sectioning may not have the same prognostic implication as results obtained from standard processing. Drs. Trattner, Reich, and Winter, using semiautomatic image analysis on early stage cervical cancers, have previously observed btumor volume does not seem to confer additional prognostic information if histopathological stage and lymph node status are knownQ [4]. While we cannot entirely exclude the possibility of occult extension, we feel that the weight of evidence supports our assertion that this case represents multi-focal stage IA1 disease. We agree with Dr. Bader and colleagues that extensive sectioning of these specimens is indicated, however, we remain unconvinced that that standard sectioning is inadequate. Rather, we assert that there is likely biologic variability which must be considered when counseling a patient considering conservative management of cancer. Sincerely, Peter A. Argenta MD
doi:10.1016/j.ygyno.2005.07.105
References To the editor: We appreciate the interest and thoughtful remarks of Dr. Bader and colleagues [1] regarding our manuscript bWidespread lymph node metastases in a young woman with FIGO stage IA1 cervical cancerQ [2]. With regard to their concerns about the adequacy of the sectioning we employed, I would first make clear that our standard procedure acquires 3 levels of each of 12 cutsections, thus generating 36 tissue specimens. In retrospect, this could have been made more clear in the manuscript, which we regret. Despite this, our total remains significantly below their recommendation of 60–80 slides per section and begs the question: would additional sectioning have revealed the tumor to be a contiguous stellate mass, and subsequently mandate upstaging? Though the question is not relevant to the management of the patient presented by virtue of her metastatic disease, it is germane to the counseling of patients considering conservative therapy for micro-invasive cervical cancer. Serial sections at 200 lm intervals would, no doubt, give additional
[1] Bader AA, Tamussino KF, Reich O, Winter R. Lymph node metastasis in FIGO stage IA1 cervical cancer? Gynecol Oncol 2005; in press. [2] Argenta PA, Kubicek GJ, Dusenberry KE, Judson PL, Downs Jr LS, Carson LF, et al. Widespread lymph node metastases in a young HIVnegative woman with FIGO stage IA1 squamous cervical cancer. Gynecol Oncol 2005;97:659 – 61. [3] Reich O, Pickel H, Tamussino K, Winter R. Microinvasive carcinoma of the cervix: site of first focus of invasion. Obstet Gynecol 2001;97:890 – 2. [4] Trattner M, Graf AH, Lax S, Forstner R, Dandachi N, Haas J, et al. Prognostic factors in surgically treated stage ib–iib cervical carcinomas with special emphasis on the importance of tumor volume. Gynecol Oncol 2001 (Jul);82(1):11 – 6.
Peter Alexander Argenta Department of Obstetrics and Gynecology, University of Minnesota, 420 Delaware St. SE, MMC 395, Minneapolis, MN 55455, USA E-mail address: [email protected]. 22 June 2005 doi:10.1016/j.ygyno.2005.07.028