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Bilateral Pelvic Lymph Node Metastases in a Case of FIGO Stage IA 1 Adenocarcinoma of the Cervix

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Bilateral Pelvic Lymph Node Metastases in a Case of FIGO Stage IA 1 Adenocarcinoma of the Cervix
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  CASE REPORTBilateral Pelvic Lymph Node Metastases in a Case of FIGO Stage IA 1 Adenocarcinoma of the Cervix Nimesh P. Nagarsheth, M.D.,* G. Larry Maxwell, M.D.,* Rex C. Bentley, M.D.,† and Gustavo Rodriguez, M.D.* ,1 *  Division of Gynecologic Oncology and   †  Department of Pathology, Duke University Medical Center, Durham, North Carolina 27710 Received October 20, 1999  Introduction.  Although the FIGO staging system has been re-cently described for microinvasive adenocarcinoma of the cervix,the precise role it will have on determining how patients aretreated remains uncertain. Using various definitions for the clas-sification of microinvasion, recent reports have suggested conser-vative management for patients with this disease. Case.  We present the case of a 62-year-old woman with FIGOstage IA 1  adenocarcinoma of the cervix found to have bilateralmicroscopic pelvic lymph node metastases. To ourknowledge, thisis the only documented case of lymph node metastases in a patientwith IA 1  disease. Conclusions.  A review of the controversial issues involving thedefinition and management of microinvasive adenocarcinoma of the cervix is presented. The finding of lymph node metastases inour patient provides support for aggressive surgical managementin selected patients with this disease.  © 2000 Academic Press INTRODUCTION The optimal management of women with microinvasiveadenocarcinoma of the cervix remains to be defined [1–3].Histologic criteria for a diagnosis of microinvasion have notbeen uniformly accepted [1, 3–8], and there have been reportsof women with apparent early-stage cervical adenocarcinomawho have had metastasis at the time of diagnosis or who havesubsequently recurred [9]. Recent reports have suggested thatselected patients with minimally invasive cervical adenocarci-noma can be managed with conservative treatment [1, 5]. Oneof these reports reviewed 21 cases of microinvasive adenocar-cinoma and found no evidence of lymph node metastases orparametrial invasion in 16 cases where radical surgery wasperformed [1]. The authors concluded that conservative sur-gery such as a cone biopsy or simple hysterectomy might be anappropriate definitive procedure for patients who meet criteriafor stage IA 1  adenocarcinoma of the cervix based on the FIGOstaging system. Similarly, another study has recently reported34 cases of invasive cervical adenocarcinoma with tumor depth  5 mm treated surgically [4]. The investigators found noevidence of extracervical disease (including no parametrial orpelvic lymph node involvement). We describe the case of apatient with stage IA 1  adenocarcinoma of the cervix who wasfound to have bilateral microscopic pelvic lymph node metas-tases at presentation. CASE REPORT The patient was a 62-year-old white woman who experi-enced menopause at 55 years of age. She had been on contin-uous estrogen and progesterone hormone replacement therapyfor the past 6 years and had been in her usual state of healthuntil May 1999 when she developed vaginal spotting over a2-week period. An endometrial biopsy performed by her pri-mary care physician was reported as “endometrial cancer.”Both a pelvic ultrasound and CT scan of the abdomen andpelvis were negative for any evidence of extrauterine disease.She was referred to the gynecologic oncology division at theDuke University Medical Center for treatment. A review of herpathology slides confirmed the outside impression of endome-trial adenocarcinoma with back to back glands in a cribriformpattern without significant mucin secretion.The patient’s medical history was significant for hypothy-roidism and hypercholesterolemia, and her previous surgeriesincluded an appendectomy and bilateral tubal ligation. Her lastmammogram and Pap smear were both within the past 6months and were normal. Obstetric history was significant forfour vaginal deliveries, with the largest baby weighing 9pounds 14 ounces. Current medications included Synthroid andPravachol. She denied any smoking or alcohol use. There wasno family history of any gynecologic cancers. Both the pa-tient’s mother and uncle had colon cancer and the patient’sfather died of lung cancer. 1 To whom correspondence and reprint requests should be addressed at theDivision of Gynecologic Oncology, Box 3079 DUMC, Duke University Med-ical Center, Durham, NC 27710. Fax: (919) 684-8719.Gynecologic Oncology  77,  467–470 (2000)doi:10.1006/gyno.2000.5786, available online at http://www.idealibrary.com on467 0090-8258/00 $35.00Copyright © 2000 by Academic PressAll rights of reproduction in any form reserved.  Review of systems revealed a stable weight, normal appetite,and no symptoms of incontinence. She denied any furthervaginal bleeding, but did complain of some vulvar burning andvaginal pressure.At admission, the general physical examination was normaland the patient weighed 63 kg. Lymph node survey was neg-ative. Abdominal examination revealed a soft, nontender, non-distended abdomen with no organomegaly and no palpablemasses. Pelvic examination revealed normal external genitaliaand the presence of a cystocele. Bimanual examination re-vealed a normal-size uterus with no adnexal masses and nopelvic nodularity. The parametrial tissues were soft. Rectalexamination was normal and guaiac negative.A urogynecology consult was obtained preoperatively. Theexamination and urodynamic studies demonstrated stage IIIpelvic organ prolapse (defined by the standardized terminologyadopted by the American Urogynecologic Society and Inter-national Continence Society [10]) with a midline anterior de-fect and urethral hypermobility.The patient subsequently underwent an exploratory laparot-omy, total abdominal hysterectomy, bilateral salpingo-oopho-rectomy, bilateral pelvic lymph node dissection, anterior col-porrhaphy, cystoscopy, and suprapubic catheter placement.Findings at the time of surgery included a normal abdominaland pelvic survey with a normal-appearing uterus, as well asnormal fallopian tubes and ovaries bilaterally. A frozen sectionperformed intraoperatively on the uterus and cervix was sus-picious for adenocarcinoma involving the endocervix withquestionable evidence of invasion. The patient had an unevent-ful postoperative course and was discharged home on Postop-erative Day 5 in stable condition.The cervix was radially sectioned and entirely submitted forhistologic evaluation, revealing an invasive endometrioid ade-nocarcinoma of the cervix (FIGO grade 2/3) which is shown inFig. 1. The depth of invasion was measured from the endocer-vical canal surface to the margin of deepest tumor penetrationand was found to be 2.5 mm in a 12-mm-thick wall. The largesthorizontal dimension was 4.0 mm, yielding a total estimatedtumor volume of 40 mm 3 . There was associated adenocarci-noma  in situ  as well as tubal metaplasia. Surgical margins werenegative and no lymphatic or vascular invasion was noted. Theendometrium, fallopian tubes, and ovaries were free of tumorbilaterally. One of six right pelvic lymph nodes and 1 of 12 leftpelvic lymph nodes were positive for microscopic metastaticadenocarcinoma (Fig. 2). Pelvic washings were negative formalignancy.The patient was referred to radiation oncology for postop-erative radiation treatment with the plan for pelvic externalbeam radiation treatment and concurrent platinum-based che-motherapy. DISCUSSION While the literature has lacked a precise universal definitionfor microinvasive cervical adenocarcinoma, the overall prog-nosis for patients with this disease appears to be excellent FIG. 1.  Cervix (H&E stain, 40  srcinal magnification) showing a moderately differentiated endometrioid adenocarcinoma located at the squamocolumnar junction. The depth of invasion as measured from the surface was 2.5 mm, with a horizontal size of 4.0 mm, yielding an estimated volume of 40 mm 3 . 468  NAGARSHETH ET AL.  [1–5]. Several studies have shown no parametrial or lymphnode invasion as well as no recurrences in patients surgicallytreated for microinvasive cervical adenocarcinoma [1, 3–5].Subsequently, there has been a trend favoring therapeuticconization as an adequate treatment option in selected patientswith microinvasive adenocarcinoma of the cervix [1, 5].The definition for stage IA 1  cervical adenocarcinoma basedon the FIGO staging system has recently been described [1].Using this definition, we were unable to find any documentedcase of microinvasive cervical adenocarcinoma that had pelviclymph node metastases. In 1985, a study reported no pelviclymph node metastases in 6 patients with cervical adenocarci-noma with less than 2 mm of invasion [2]. While 2 of 18patients with lesions involving 2 to 5 mm of invasion (mea-sured from the mucosal surface) and 2 of 7 patients withlesions involving 5 to 10 mm of invasion did have lymph nodemetastases, none of these patients had tumor smaller than 2 cmin greatest dimension. The authors demonstrated a poorerprognosis in patients with lymph node metastases as 9 of 10patients with documented nodal disease went on to developdiffuse distant metastases and/or abdominal carcinomatosis.In an attempt to better predict which patients are at risk forlymph node spread, a study compared the relationship of tumorvolume and depth of invasion with lymph node metastasis [8].Using the definition of microinvasive adenocarcinoma as tu-mor volume less than 500 mm 3 , none of 22 microinvasivetumors had detectable lymph node involvement. Of the remain-ing larger tumors (  500 mm 3 ), 2 of 5 patients with up to 5 mmof invasion (measured from the surface of the endocervicalepithelial lining to the deepest detectable malignant cells) and4 of 11 patients with tumors containing greater than 5 mm of invasion (stage I) did have lymph node metastasis. The authorsconcluded that volume of tumor, rather than depth of invasion,may provide a better predictor of lymph node metastasis instage I cervical adenocarcinoma.Although the definition and management of microinvasivecervical adenocarcinoma remains controversial, we are notaware of any previously documented case of lymph nodemetastases in a patient with FIGO stage IA 1  adenocarcinoma of the cervix. While we cannot derive any conclusions from thissingle case, we demonstrate that lymph node metastases mayexist in the setting of microinvasive adenocarcinoma. There-fore, aggressive surgical management should be consideredwhen treating patients with this disease. Further studies will beneeded to determine the precise role that the FIGO stagingsystem will have on both the definition and management of microinvasive adenocarcinoma of the cervix. REFERENCES 1. Schorge JO, Lee KR, Flynn CE, Goodman A, Sheets E: Stage IA 1  cervicaladenocarcinoma: Definition and treatment. Gynecol Oncol 93:219–222,19992. Berek JS, Hacker NF, Fu Y, Sokale JR, Leuchter RC, Lagasse LD:Adenocarcinoma of the uterine cervix: Histologic variables associatedwith lymph node metastasis and survival. Obstet Gynecol 65:46–52, 1985 FIG. 2.  Right pelvic lymph node (H&E stain, 100  srcinal magnification) showing small microscopic deposits of metastatic adenocarcinoma histologicallysimilar to the cervical primary. The positive lymph node from the left side had a similar appearance. 469 CASE REPORT  3. Kaku T, Kamura T, Sakai K Amada S, Kobayashi H, Shigematsu T, SaitoT, Nakano H: Early adenocarcinoma of the uterine cervix. Gynecol Oncol65:281–285, 19974. Kinney WK, Keene GL, Hodge DO, Webb ML, Podratz KC: Microinva-sive adenocarcinoma of the cervix: Does it exist? Gynecol Oncol 74:320,1999 [abstract]5. Ostor A, Rome R, Quinn M: Microinvasive adenocarcinoma of thecervix: A clinicopathologic study of 77 women. Obstet Gynecol 89:88–93, 19976. Nguyen G, Jeannot AB: Exfoliative cytology of in situ and microinvasiveadenocarcinoma of the uterine cervix. Acta Cytol 28:461–467, 19847. Qizilbash AH: In-situ and microinvasive adenocarcinoma of the uterinecervix. Am J Clin Pathol 64:155–170, 19758. Kaspar HG, Dinh TV, Doherty MG, Hannigan EV, Kumar D: Clinicalimplications of tumor volume measurement in stage I adenocarcinoma of the cervix. Obstet Gynecol 81:296–300, 19939. Coppleson M: Gynecologic Oncology, London, Churchill Livingstone,1992, pp 644–64510. Bump RC, Mattiasson A, Bo K, Brubaker LP, DeLancey JO, Klarskov P,Shull BL, Smith AR: The standardization of terminology of female pelvicorgan prolapse and pelvic floor dysfunction. Am J Obstet Gynecol 175:10–17, 1996 470  NAGARSHETH ET AL.
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