“Primary peritoneal” high-grade serous carcinoma is very likely metastatic from serous tubal intraepithelial carcinoma: Assessing the new paradigm of ovarian and pelvic serous carcinogenesis and its implications for screening for ovarian cancer

doi:10.1016/j.ygyno.2010.11.020

Gynecologic Oncology

Volume 120, Issue 3, March 2011, Pages 470-473

https://doi.org/10.1016/j.ygyno.2010.11.020 Get rights and content

Abstract

Objective

Primary peritoneal high-grade serous carcinoma is thought to arise from the peritoneum, but recent data suggest that the fallopian tube may be an occult source of many of these tumors. This study was performed to evaluate this hypothesis in an unselected series of cases.

Methods

Fallopian tubes from 51 consecutive cases meeting the GOG criteria for primary peritoneal high-grade serous carcinoma, FIGO stages II–IV, were analyzed.

Results

Serous tubal intraepithelial carcinoma (STIC) was identified in 19 patients (37%). When the fimbriae were examined, STIC was identified in 46%, and when all tubal tissue was examined, 56%. STIC was confined to the fimbriae in 53%, involved fimbriae and nonfimbrial mucosa in 20%, and was confined to nonfimbrial mucosa in 20%. Patients with STIC were significantly older than those without STIC (75 years vs. 67 years, respectively; p = 0.007). Patients with STIC were significantly more likely to have FIGO stage IV disease as compared to those without STIC (42% vs. 12.5%, respectively; p = 0.037).

Conclusions

At least half the cases of primary peritoneal high-grade serous carcinoma are associated with intraepithelial carcinoma of the fallopian tube, usually involving the fimbriae. These findings support the view that, like “primary ovarian carcinoma,” what has been traditionally classified as “primary peritoneal carcinoma” is probably derived from occult high-grade serous carcinoma in the fallopian tube. These findings have important implications for ultrasound screening trials for ovarian cancer which are based on the assumption that an enlarged ovary is a very early manifestation of disease.

Research highlights

►Tubal intraepithelial carcinoma is seen in 37% of women with peritoneal carcinoma. ►The tubal fimbrial mucosa may be the site of origin of “peritoneal” serous carcinoma. ►Findings support the new paradigm indicating tubal origin of pelvic serous carcinoma.

Introduction

Our understanding of ovarian carcinogenesis has been evolving over many years. It has been known for decades that in about 10% of cases of serous carcinomatosis of extrauterine origin, the ovaries are normal in size or only slightly enlarged and display only surface involvement, limited cortical involvement, or may even be without tumor. Since no other primary site is generally evident in these patients, it has been presumed that the peritoneum is the source. This interpretation is supported by the occasional serous carcinoma found in a few women who had TAH-BSO in the remote past.

As interest in ovarian carcinogenesis has been high due to the high mortality rate associated with ovarian carcinoma, pathologists have looked more and more carefully at the pathologic specimens both grossly and microscopically. In our experience, the closer one looks at serous “ovarian” cancers, the less clear it becomes that the ovary is in fact the primary site. Accordingly, more and more serous carcinomas have been classified as primary peritoneal carcinomas, from 10% historically, to 18–28% in the last decade [1], [2], [3].

Recent studies have examined the tubal fimbriae in women with serous ovarian carcinoma and have found serous tubal intraepithelial carcinoma (STIC) in a substantial proportion of cases [4], [5]. If STIC is the precursor of apparent “ovarian” serous carcinoma, then it would appear even more likely that STIC is the origin of serous carcinomas that do not appear to be arising in the ovary; i.e., those classified as primary peritoneal serous carcinoma. The current study was designed to determine how often primary peritoneal serous carcinomas are associated with STIC in a large unselected series of advanced stage high-grade serous carcinoma that were classified as primary peritoneal tumors using the established GOG criteria [6].

Section snippets

Methods

All consecutive ovarian and peritoneal carcinomas accessioned from 1991 to 2010 at the Washington Hospital Center were reviewed. Criteria for diagnosis of primary peritoneal serous carcinoma as described by the GOG were as follows [6]:

1.
Both ovaries must be normal sized or enlarged by a benign process
2.
Extraovarian involvement must be greater than ovarian involvement
3.
The ovarian component must be either (a) nonexistent, (b) confined to the surface with no cortical invasion, or (c) ovarian surface

Results

A total of 63 high-grade serous carcinomas and 2 carcinosarcomas met the GOG criteria for primary peritoneal carcinoma. Sections of fallopian tube were available for examination in 51 patients. In 35 cases, the fimbriae were present, and in 9 cases, the tubes were embedded in their entirety.

The results are shown in Table 1, Table 2, Table 3. STIC was identified in 19 patients (37%) and was bilateral in 6. All cases tested showed strong positive nuclear staining for p53 (Fig. 3). In 10 patients,

Discussion

The precursor of high-grade serous carcinoma, the most common type of ovarian cancer and the one responsible for most ovarian cancer deaths, has been sought for decades without success. High-risk ovaries, including normal-appearing ovaries contralateral to or adjacent to carcinomas, ovaries prophylactically removed in patients with a BRCA mutation or a family history of ovarian cancer, and normal-appearing ovaries in women with primary peritoneal carcinoma have been studied by many

Conflict of interest statement

The authors declare that there are no conflicts of interest.

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N <sup>o</sup> 377- Indications gynécologiques bénignes de l'hystérectomie
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Aider les médecins qui pratiquent la chirurgie gynécologique dans leur processus décisionnel relatif aux indications bénignes de l'hystérectomie.
Médecins, y compris gynécologues, obstétriciens, médecins de famille, chirurgiens généralistes, urgentologues; infirmières, y compris les infirmières autorisées et les infirmières praticiennes; apprentis en médecine, y compris étudiants de médecine, résidents, stagiaires (fellows); et autres fournisseurs de soins de santé.
Femmes adultes (18 ans et plus) qui devront subir une hystérectomie pour une indication gynécologie bénigne.
La présente directive clinique examine les différentes voies d'abord de l'hystérectomie et l'utilité des interventions chirurgicales concomitantes.
Pour la présente directive clinique, des recherches ont été effectuées dans les bases de données PubMed, Medline et Cochrane Library pour trouver des études pertinentes. Les recherches ont été effectuées parmi les publications des cinq dernières années (2012-2017) au moyen des termes de recherche MeSH suivants ainsi que leurs variations : vaginal hysterectomy, laparoscopic hysterectomy, robotic hysterectomy, laparoscopically assisted vaginal hysterectomy, total laparoscopic hysterectomy, standard vaginal hysterectomy et total vaginal hysterectomy.
Le contenu et les recommandations ont été rédigés et acceptés par les auteurs principaux et membres du comité de pratique clinique – gynécologie. Le conseil d'administration de la Société des obstétriciens et gynécologues du Canada a approuvé la version définitive aux fins de publication. La qualité des données probantes utilisées dans le présent document a été évaluée au moyen des critères du cadre méthodologique GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) (tableau 1, tableau 2). Le résumé des conclusions est disponible sur demande.
Bien que l'hystérectomie soit commune, la pratique chirurgicale varie grandement chez les médecins spécialisés en gynécologie. La présente directive expose les facteurs pré- et périopératoires à prendre en compte pour améliorer la qualité des soins prodigués aux femmes qui doivent subir une chirurgie pour une affection gynécologique bénigne.
La présente directive clinique de la Société des obstétriciens et gynécologues du Canada sera automatiquement passée en revue cinq ans après sa publication. Les auteurs peuvent toutefois proposer une autre date de réévaluation s'ils croient qu'une période de cinq ans est trop courte ou trop longue en fonction de leurs connaissances du sujet à titre d'experts en la matière.
La présente directive clinique a été élaborée au moyen de ressources financées par la Société des obstétriciens et gynécologues du Canada.
- 1
  La technicité correspond à la proportion des hystérectomies réalisées par voie d'abord à effraction minimale (laparoscopique, assistée par laparoscopie et vaginale). L'indice de technicité élevé est lié à une amélioration de la qualité chirurgicale et des soins à la patiente (élevée).
- 2
  Les voies d'abord de l'hystérectomie à effraction minimale sont liées à moins de complications périopératoires que la laparotomie (élevée).
- 3
  Les hôpitaux et chirurgiens qui traitent un grand nombre de patientes sont les plus susceptibles de détenir un indice de technicité élevé et un taux plus faible de complications (élevée).
- 4
  Les protocoles de chirurgie d'un jour pour l'hystérectomie à effraction minimale sont rentables, n'augmentent pas les taux de complications ni de réadmission et sont liés à un taux élevé de satisfaction des patientes (moyenne).
- 5
  Le risque de traumas des voies urinaires est comparable entre les différentes voies d'approche chirurgicales de l'hystérectomie (moyenne).
- 6
  La laparotomie ou la mini-laparotomie peut être indiquée comme solution de remplacement dans des cas précis en fonction de facteurs propres à la patiente, des indications chirurgicales et des pathologies sous-jacentes (moyenne).
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  Le risque de déhiscence de la tranche vaginale est rare et n'est pas lié au choix du matériel de suture ni à la voie de fermeture (moyenne).
- 8
  L'hystérectomie supracervicale n'a pas démontré qu'elle peut préserver la fonction sexuelle, diminuer le risque de prolapsus des organes pelviens, ni réduire l'incidence du trauma des voies urinaires par rapport à l'hystérectomie totale (moyenne).
- 9
  Chez les femmes qui présentent des fibromyomes utérins, un traitement médicamenteux préopératoire à l'acétate de leuprolide ou à l'acétate d'ulipristal peut réduire la taille des myomes, diminuer les saignements et corriger l'anémie. Les risques et avantages du traitement médicamenteux doivent être abordés avant l'intervention (élevée).
- 10
  La préparation mécanique systématique des intestins n'est pas nécessaire avant une chirurgie gynécologique pour une maladie bénigne (élevée).
- 11
  L'ablation des ovaires normaux lors d'une hystérectomie réduit le risque de cancer de l'ovaire, mais peut entraîner des répercussions sur la santé. L'ovariectomie bilatérale peut provoquer une manifestation aiguë de symptômes ménopausiques chez les femmes non ménopausées; elle n'a démontré aucun avantage de survie en l'absence d'une prédisposition génétique au cancer de l'ovaire (élevée).
- 12
  L'hystérectomie seule affecte la réserve ovarienne (élevée).
- 13
  La salpingectomie prophylactique lors de l'hystérectomie devrait diminuer l'incidence des cas de cancer de l'ovaire grave de haut grade (faible).
- 14
  Il n'y a aucune donnée probante solide à l'appui de la suspension systématique aux utéro-sacrées ou de la voûte vaginale lors de l'hystérectomie chez les femmes qui ne présentent pas de prolapsus des organes pelviens (faible).
- 1
  Pour les indications gynécologiques bénignes, l'hystérectomie devrait se faire de préférence par voie d'abord vaginale ou laparoscopique (forte, élevée).
- 2
  Pour réaliser une hystérectomie, la voie d'abord vaginale est toujours l'option privilégiée, mais la chirurgie laparoscopique est une option de remplacement (forte, moyenne).
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- 6
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- 7
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- 8
  Pour les patientes atteintes d'endométriose qui prévoient de subir une hystérectomie, l'excision complète des lésions endométriosiques doit être effectuée au moment de l'intervention (forte, moyenne).
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To assist physicians performing gynaecologic surgery in decision making surrounding hysterectomy for benign indications.
Physicians, including gynaecologists, obstetricians, family physicians, general surgeons, emergency medicine specialists; nurses, including registered nurses and nurse practitioners; medical trainees, including medical students, residents, and fellows; and all other health care providers.
Adult women (18 years and older) who will undergo hysterectomy for benign gynaecologic indications.
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The content and recommendations were drafted and agreed upon by the principal authors and members of the Gynaecology Committee. The Board of the Society of Obstetricians and Gynaecologists of Canada approved the final draft for publication. The quality of evidence was rated using the criteria described in the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology framework (Tables 1 and 2). The Summary of Findings is available upon request.
Hysterectomy is common, yet surgical practice still varies widely among gynaecologic physicians. This guideline outlines preoperative and perioperative considerations to improve the quality of care for women undergoing benign gynaecologic surgery.
This Society of Obstetricians and Gynaecologists of Canada clinical practice guideline will be automatically reviewed 5 years after publication. However, authors can propose another review date if they feel that 5 years is too short/long based on their expert knowledge of the subject matter.
This guideline was developed with resources funded by the Society of Obstetricians and Gynaecologists of Canada.
- 1
  Technicity is defined as the proportion of hysterectomies performed by a minimally invasive route (laparoscopic, laparoscopic-assisted, and vaginal). Increased technicity index is associated with improved surgical quality and patient care (High).
- 2
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- 3
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- 4
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- 1
  Hysterectomy for benign indications should preferably be approached by either vaginal or laparoscopic routes (Strong, High).
- 2
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- 7
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- 8
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“Primary peritoneal” high-grade serous carcinoma is very likely metastatic from serous tubal intraepithelial carcinoma: Assessing the new paradigm of ovarian and pelvic serous carcinogenesis and its implications for screening for ovarian cancer

Abstract

Objective

Methods

Results

Conclusions

Research highlights

Introduction

Section snippets

Methods

Results

Discussion

Conflict of interest statement

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Curr Op Obstet Gynecol

The tubal fimbriae is a preferred site for early adenocarcinoma in women with familial ovarian cancer syndrome

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