ADENOMIOSI ED ENDOMETRIOSI: DUE ENTITA DISTINTE?

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1 ENDOMETRIOSI: dalla ricerca nuove prospettive per comprendere la malattia 27 gennaio 2017 CENTRO CONGRESSI GIOVANNI XXIII-Bergamo ADENOMIOSI ED ENDOMETRIOSI: DUE ENTITA DISTINTE? Liliana Mereu MD, PhD Responsabile U.S. Ginecologia OSPEDALE S CHIARA di TRENTO

ADENOMIOSI: Definition In 1860 ROKITANSKY described cystosarcoma adenoid uterium In 1896 Von Recklinghausen distinguished two entity: intra and extra

adeno) In 1925 FRANKL used the term adenomyosis : the direct connection of the endometrium with the islands of mucosa located in the muscolature can

2 ADENOMIOSI: Definition In 1860 ROKITANSKY described cystosarcoma adenoid uterium In 1896 Von Recklinghausen distinguished two entity: intra and extra uteri In 1908 Cullen described the different appearances (suberitoneal, submucosas, intrauterine) 1921: new pathology entity: ADENOMYOMA (endo + adeno) In 1925 FRANKL used the term adenomyosis : the direct connection of the endometrium with the islands of mucosa located in the muscolature can be established in serial sections SAMPSON created the word endometriosis to describe the presence of islets of uterine mucosa in the peritoneal cavity

microscopically exhibits ectopic non-neoplastic, endometrial gland

3 ADENOMIOSIS: Definition The benign invasion of endometrium into the myometrium producing a diffusely enlarged uterus which microscopically exhibits ectopic non-neoplastic, endometrial gland and stroma surrounded by the hyperetrophic and hyperplastic myometrium Bird et al 1972

4 HISTOLOGICAL DEFINITION Glandular extension below the endometrial-myometrial interface (EMI) > 2.5 mm (Kurman, 1994) Basal Endometrium 1 mm 5 mm Myometrial Junctional Zone Endometrial Myometrial Interface EMI

5 Adenomyosis: AP criteria Benagiano et al 2015

6 DIAGNOSIS The diagnosis of adenomyosis depends on - the thresholds used by individual pathologist - concomitant pathologies - Variants: superficial adenomyosis stromal adenomyosis Incomplete adenomyosis adenomiosis with sparse gland Seidman et al 1996

7 HYSTOLOGICAL TYPES DIFFUSE FOCAL: adenomyoma cystic adenomyosis POLYPOID ADENOMYOMAS: typical atypical OTHER: adenomyoma of the endocervical type retroperitoneale adenomyoma Gilks CB, 2000 Grimbizis GF, 2008 Takeuchi H, 2010 Mazur MT 1981 Gilks CB 1996

Pathogenesis: theories INVAGINATION of the endometrium in the myometrium due to tissue trauma DE NOVO from embryonic misplaced pluripotent Mullerian remnants METAPLASIA OF PLURIPOTENT STERM CELL

8 Pathogenesis: theories INVAGINATION of the endometrium in the myometrium due to tissue trauma DE NOVO from embryonic misplaced pluripotent Mullerian remnants METAPLASIA OF PLURIPOTENT STERM CELL Throw lymphatic system Bone Marrow cell presents in the vasculature Mesenchimal Pale cells Cullen 1908 Ferenczy et al 1998 Javert 2051 Garcia 2011 Sasson 2008 Ibrahim 2015 HYPERESTROGENISM - Presance of P450 aromatase prot - action of aromatase on androgen precursor - action of aromatasi on estrone sulfatase - higher estrone - higher E2 level in mestrual blood Kitavaki 1997, Yamamoto 1985 Ezaki 2001, Takahashi 1989, Kitawaki 2001

9 Risk Factors Multiparity Pelvic surgery Dilatation and Curretage Early menarche Obesity Hyper estrogenism Tamoxifen Smoking Parazzini 2009, Vercellini 2006, Templeman 2000

Prevalence and symptoms 5-70% of surgically removed uteri 70-80% cases in women in the 40-50 5-25% cases in women younger than 39 5-10% cases in women older than 60 Endometriosis is observed in 6-22%

10 Prevalence and symptoms 5-70% of surgically removed uteri 70-80% cases in women in the % cases in women younger than % cases in women older than 60 Endometriosis is observed in 6-22% of cases Myomas are observed in 35-55% of cases 50% menorrhagia 30% dysmenorrhea 20% metrorrhagia Dyspareunia Chronic pelvic pain Kim and Straw et al, 2000 Bazot et al, 2001, Vercellini et al,1995 Benagiano et a,l 2012 Ferenczy 1998 Bergeron 2006

11 ADENO ENDO: similarities Similarities: definition symptomathology Estrogen-dependency Inflammation Molecular aberrations Endometrial Immunology and gene expression Pathofisilogical connections 20% with endo had adeno (Di Donato 2014) 48-77% with DIE had adeno (Lazzeri, 2014, Chapron et al) 66% focal adeno (Chapron et al) Extensive endo + adeno appear early reprod life (Green 2009, Chapron 2011)

12 ADENO-ENDO: Differences After decades of debate and numerous studies it is now well accepted that adenomyosis DOES NOT REPRESENT a SUB-ENTITY, the differences are: - Pathogenesis - Adenomyosis may represents a unique form of endometrial diverticulis - Adenomyosis mostly made up of non-functional (BASAL) endometrium and is frequently connected with the mucosa - may occur independently of each other - Timing of clinical manifestation

Juvenil Adenomyosis Whereas endometriosis can manifest itself in young adolescents and even before and can progress rapidly the rare juvenile adenomyosis is characterised by localized cyst, rather

13 Juvenil Adenomyosis Whereas endometriosis can manifest itself in young adolescents and even before and can progress rapidly the rare juvenile adenomyosis is characterised by localized cyst, rather than the presence of classic features Cyst up to 3 cm with haemorrhagic content Histologically:these cysts are lined with an endometrial-like layer. The smooth muscle cells surrounding the cyst show hyperplasia, macrophage infiltration and haemosiderin pigmentation. Brosens et al 2014

14 ADENO and INFERTILITY Disruption and thickening of the myometrial junctional zone can result in perturbed uterine peristalsis Biochemical and functional alterations have been identified in both eutopic and heterotopic endometrium may lead to lower receptivity The presence of an abnormal concentration of intrauterine free radicals and of altered decidualization A higher spontaneous abortion rate Negative effect on the outcome of IVF ICSI, leading to reduced rates of clinical pregnancy and implantation and an increased risk of early pregnancy loss. Kunz et al 2005, 2007; Benagiano et al 2012, Iagarashi et al 2002, Ota et al 1999; Chiang 1999, Vercellini et al20014

15 Adenomyosis and Pregnancy Benagiano et al 2015

16 Obstetrics complications

17 ADENO + ENDO 227 women +/- endometriosis MRI evaluation of the uterus They subdivided women into four groups (17 24, 25 29, 30 34, > 34) OBJECTIVE: Relation to the age of the women and the subsequent appearance of adenomyosis. RESULTS - prevalence of diffuse and focal adenomyosis: 79% of all patients with endo 90% in women younger than 36 years, 28% in no endo group 9% in healthy control group. - Found an increased diameter of the dorsal junctional zone of the uterus (a feature considered indicative of the invasion of basal endometrium into the junctional zone and therefore of incipient adenomyosis), had already commenced early in the third decade. - In women WITH endometriosis, this phenomenon progressed steadily - In women WITHOUT endometriosis, there was almost no sign of adenomyosis up to the age of 34 years. Kunz et al 2007

18 ADENO + ENDO: natural hystory Endometriosis and adenomyosis may coexist Endometriosis usually becomes clinically evident at an age lower than that of adenomyosis Adenomyois is a disease of the adults The alterations leading to adenomyosis may start early, but usually become manifest only after the age of 30 years Kunz et al 2007

19 ADENO - ENDO È di estrema importanza clinica la diagnosi endometriosi + adenomiosi quando presente Corretta presa in carico della paziente Corretto counselling Corretta scelta terapeutica.

20 Diagnosis

21 Therapy SURGICAL: hysterectomy Adenomyoma resection ISC ablation ALTERNATIVE CONSERVATIVE TREATMENT: UA embolization US-MRI Focal electrocoagulation MEDICAL: Levonorgestrel IUD Danazol GnRH agonist Inibitori aromatasi E/P pills Antioxidant

22 ADENO + ENDO association ADENOMYOSIS + INTESTINAL ENDO INTESTINAL ENDO

23 Adenomyosis and Endometriosis DISMENORREA

24 Darai et al., 2005 Landi et al., 2008 Ferrero et al., 2009 Stepniewska et al., 2010

25 CONCLUSIONI Adenomiosi ed endometriosi sono DISTINTE in termini di - Anatomia patologica - Teorie Patogenetiche - Fattori di rischio - Frequenza nelle diverse età Ma sono strettamente CORRELATE per - definizione - aumento spessore zona giunzionale miometriale - alterazioni biochimiche dell endometrio eutopico ed eterotopico - associazione - sovrapposizione di sintomi

26 CONCLUSIONI CORRETTA DIAGNOSI ORIGINE COMUNE STESSE ENTITA ORIGINE NON COMUNE DIVERSE ENTITA CORRETTO PIANO TERAPEUTICO

27 GRAZIE PER L ATTENZIONE

2/24/19. Myometrial evaluation. Size Echotexture. Homogeneous Heterogeneous. Adenomyosis Fibroids. Adenomyosis. MUSA guidelines

2/24/19. Myometrial evaluation. Size Echotexture. Homogeneous Heterogeneous. Adenomyosis Fibroids. Adenomyosis. MUSA guidelines Content Adenomyosis and MUSA guidelines for myometrial disorders Adenomyosis MUSA guidelines Dr Lufee Wong FRANZCOG, MPH, DDU Recommended reporting guidelines Fibroids Adenomyosis Myometrial evaluation