{"paper_id":"46d64f97-d0b6-4dd0-95c0-f48c6e83c581","body_text":"Research Article\nClinical Obstetrics, Gynecology and Reproductive Medicine\nClin Obstet Gynecol Reprod Med, 2019        doi: 10.15761/COGRM.1000260\n Volume 5: 1-6\nISSN: 2059-4828\nNeuro-etiologic classification of adenomyosis: the \n“Shanghai system”\nZhang Lin Na, Chen Lan, Xu Hong, Wang Yuan, Zhang Hui Juan and MJ Quinn*\nDepartments of Gynaecology & Pathology, Shanghai Jiao Tong University, China\nAbstract\nSome patterns of uterine adenomyosis (AM) are more common in China than Europe or USA.   In this new classification derived from clinical observations in \nShanghai, there are four patterns of adenomyosis, and, three out of the four have neurologic abnormalities associated with specific injuries to uterotubal nerves \n\"Shanghai system\" (SS), types 1-4, AM).  Typically, European or US women present with “painful” uterine bleeding in their 30-40’s that results in hysterectomy at \nreduced uterine weights (80-150g).  Histology shows aberrant reinnervation throughout the body of the uterus and uterosacral ligaments, as a result of intrapartum \ninjuries, or, excessive traction applied to the cervix, or, over-vigorous curettage (SS, type 2, AM).  \nIn Shanghai there are two common variations that have very different clinical presentations.  The first is diffuse, symmetric adenomyosis (SS, type 1, AM) where \nwomen present with “painless”, pelvic masses weighing 250-1250g.  Laparoscopy shows complete avulsion of their uterosacral-cardinal ligament complexes, and, \nhistologic examination shows there are no nerves in their uteri or Fallopian tubes.  The second variation is a focal adenomyoma occupying the upper half of the \nuterus that may also be come very large over the course of a reproductive career (SS, type 3, AM).  These women have torn nerve fibers in their uterosacral ligaments \nassociated with paracervical infiltration of local anesthesia and subsequent traction to the cervix during outpatient evacuation of the first trimester uterus.  The result \nis a focal adenomyoma, typically, in the postero-superior surface of the uterus.  Embryologic, or, pedunculated, or, polypoid patterns may contribute a fourth, non-\nneurologic pattern of adenomyosis (SS, type 4, AM).  \nThis account provides clinical, laparoscopic, radiologic and histologic evidence for each of these neurologic injuries.  Many are preventable by simple amendments to \nclinical policies or surgical techniques.\n*Correspondence to: MJ Quinn, Dept OBGYN, Shanghai Jiao Tong University, \nInternational Peace, Maternity and Child Health Hospital, 910 Hengshan Road, \nXujiahui, Shanghai, China, PR 200030, E-mail: mjquinn001@icloud.com\nReceived: August 02, 2019; Accepted: August 16, 2019; Published: August 19, \n2019\nIntroduction\nIn 1908, TS Cullen classified adenomyosis into three distinctive \nsubtypes of adenomyosis based on morphologic appearances [1]. He \ndescribed: \n(i) smooth enlargement of the uterus without disturbing its contour, \n(SS, type 1 or type 3, AM) \n(ii) subperitoneal or intraligamentary adenomyomata, (SS, type 4, AM)\n(iii) submucous adenomyomata. (SS, type 3, AM)\nIt is now clear to us in Shanghai, that there are two, common \npatterns of adenomyosis in China that are relatively unusual in Western \ncountries though TS Cullen illustrated both types in his book under \nthe category “smooth enlargement of the uterus without disturbing its \ncontour” [2]. The most distinctive is diffuse, symmetric, adenomyosis \nthat usually presents as a painless mass (250-1250g) with symptoms of \n“pressure” on adjacent organs. \"Shanghai system\" (SS), Type 1, AM,). \nHistologic examination shows there is no evidence of nerves anywhere \nin either the uterus, or Fallopian tubes [2] (Figure 1A-F). In a second, \ncommon, clinical presentation in Shanghai, there may be extreme \nenlargement of a focal posterior wall adenomyoma that produces \nmarked distortion of the uterine cavity, asymmetry of the uterus, and \noften, uterine retroversion (Figure 3E-F , type 3, AM, SS). The clinical \npresentation is also usually painless, with some asymmetry of the \nuterosacral ligaments, and, on histologic examination there are no \nnerves in the myoma. Both are relatively rare presentations in UK or \nUS gynecology. \nThe best evidence in the US literature for the etiology of \nadenomyosis derives from the observation that vigorous curettage of \none horn of the uterus of a pregnant rabbit produces adenomyosis, \nwhilst allowing the pregnancy to continue in the opposite horn [3]. This \nis the “trauma” hypothesis which is reinforced by radiologic interest in \nthe width of the endometrial- myometrial interface (or, junctional zone \n(JZ) of the uterus). Twelve millimeter thickness of the JZ guarantees \na histologic diagnosis of adenomyosis though others discuss different \ndegrees of sensitivity and specificity at different thicknesses [4,5]. These \nradiologic colleagues, however, make no mention of the endometrial-\nmyometrial nerve plexus described by Krantz [6] that postdates many \nof the classic descriptions of adenomyosis in the US literature [3,7], and \nis not mentioned in more recent updates [8,9]. If there is interruption \nof this nerve plexus either by direct trauma at curettage, or, through \nuterine tachysystole, or, through injuries to the uterotubal nerves that \npass through the uterosacral ligaments to supply it, then each may \ncontribute to loss of innervation in different parts of the uterus and \nFallopian tubes. Tubal ligation and Cesarean section have both been \ndiscussed in the context of the etiology of adenomyosis. Tubal ligation \nmay increase intrauterine pressures at different times of the menstrual \ncycle [10] whereas a myometrial incision (above the lower segment of \n\nLin Na Z (2019) Neuro-etiologic classification of adenomyosis: the “Shanghai system”\nClin Obstet Gynecol Reprod Med, 2019        doi: 10.15761/COGRM.1000260\n Volume 5: 2-6\nthe uterus) may injure endometrial-myometrial nerves, or, tearing one, \nor both, angles of the uterine incision may do the same ? [11] Some \nseries of US patients refer to uterine weights of greater than 250g with \nthe highest recorded weight of 705 g but they are rare [3]. Typically, \nUS women present with painful  periods that require hysterectomy \nat uterine weights of 80-150g (type 2, AM, SS) that are common in \nWestern clinical practice, though not mentioned in Cullen’s original \naccount. They is no published evidence for significant numbers of cases \nof diffuse, painless adenomyosis (SS, type 1, AM) and focal, painless \nadenomyosis (SS, type 3, AM), that we frequently observe in Shanghai ?\nThe nerve supply of the uterus\nAs undergraduates we saw cadaveric material preserved in \nformalin (that destroys autonomic nerves) whereas Lee used alcohol \nin his dissections [12,13]. In an alcohol-embalmed cadaver the full \nmorphology of the pelvic plexi is clear [14] as the nerves pass through \nthe fan of the uterosacral-cardinal ligament plexus to converge on the \nvaginal vault where they are susceptible to injury through difficult \nfirst labors, physical efforts during defaecation, and, complications \nof the management of evacuation of the uterus through surgical and \nmedical techniques [15]. Partial, or complete, injuries to the uterosacral \nligaments results in partial, or complete, injuries to the uterotubal \nnerves with differing degrees of aberrant reinnervation depending \non the extent of the injury [15]. The distal third of the Fallopian tubes \nreceives nerve supply from the ovarian plexus through the free edge of \nthe mesosalpinx [16]. \nIn this discussion it is both the intrauterine, and extrauterine, \nnerve supply that assumes significance in relation to different patterns \nof adenomyosis. Within the uterus mixed nerve bundles delivered (a) \nin the uterosacral ligaments, and, (b) along with the uterine artery, \nform the endometrial-myometrial nerve plexus and subserosal nerve \nplexus, respectively, that reflects the differing embryologic origins of \nthe endometrium and myometrium [6,17]. Both deliver sparse nerve \nbundles to the myometrium though normal endometrium does not \ncarry a nerve supply. Intra-uterine injuries to the nerve supply will \ncause collateral sprouting of nerve bundles and aberrant reinnervation \nof injured nerves (Figure 2C-D) whereas pre-uterine injuries to nerves \nin the uterosacral ligaments may demonstrate loss of nerves in adjacent \nnerve bundles (Figure 3C-D). The two patterns of injury are separate \nand distinctive.\nFigure 1(A-F). Type 1, diffuse, symmetric, painless adenomyosis. (A) Diffuse, symmetric \nadenomyosis at uterine weight of 260g. (B) Complete absence of uterosacral ligaments at \nlaparoscopy. (C) Complete loss of the endometrial-myometrial nerve plexus (anti-S100, \nx100). (D) Complete loss of uterotubal nerves throughout the resected specimen. (E) \nDiffuse, symmetric adenomyosis (T2 weighted, MR scan, LS). (F) Diffuse, symmetric \nadenomyosis (T2 weighted, MR scan, TS).\nFigure 2(A-F). Type 2, irregular, asymmetric, painful adenomyosis. (A) Irregular, \nasymmetric, painful in uterus weighing less than 150g. (B) Irregular scarring of uterosacral \nligaments at laparoscopy. (C) Aberrant reinnervation of endometrial-myometrial interface \n(anti-S100, x 100). (D) Aberrant reinnervation in the uterosacral ligaments (anti-S100, \nx100). (E) Irregular, asymmetric adenomyosis with enlarged cervix and Cesarean scar on \nthe anterior uterine wall (T2, weighted MR scan, LS). (F) High signal intensity of injured \nuterosacral ligaments on either side of the cervix (T2 weighted, MR scan, coronal section)\n\nLin Na Z (2019) Neuro-etiologic classification of adenomyosis: the “Shanghai system”\nClin Obstet Gynecol Reprod Med, 2019        doi: 10.15761/COGRM.1000260\n Volume 5: 3-6\nPrevious classifications of adenomyosis\nA number of classifications of the varying clinical phenotypes \nof adenomyosis have been set out. KF von Rokitansky identified the \ncondition in 1860 with one of the original, light microscopes [18] \nthough it was TS Cullen (1908) who presented the first classification of \nadenomyosis based largely on macroscopic and microscopic studies of \nthe condition [1]. John Sampson (1921) discussed a similar classification \nto that of TS Cullen [19]. More recently, there have been two clinical \ncontributions to attempt to improve the classification of adenomyosis; \nDr Kishi (KS) in Takanohara Hospital, Nara, Japan discussed four \nsubtypes of adenomyosis based on magnetic resonance imaging [20], \nand, Dr. Bazot (BZ), at Tenon Hospital, Paris, who described three \ndifferent patterns of adenomyosis using vaginal sonography and MR \nimaging [21]. There are some minor differences between the two \nclassifications but both are based on specific, radiologic appearances \n(Table 1).\nThe “Kishi” classification, 2012 (Table 1A)\nIn 152 women undergoing MRI, Kishi [20] described four subtypes \nof adenomyosis (Table 1A). In their stepwise regression analysis, Kishi \net al. noted that a significant proportion of type 1 adenomyosis (KS \n1) had prior terminations of pregnancy whereas type 2 (KS 2) did not \n(32.2% v 7.8%), they proposed that a “barrier” exists at the endometrial-\nmyometrial interface which prevents adenomyosis, and, this barrier \nmay be injured by pregnancy or curettage. In type 3 adenomyosis \n(KS 3), clinical features included menorrhagia (18/22, 81.8%) and \ndysmenorrhea (18/22, 81.8%). They suggested that this is a “de novo \nproduct” of embryologic or metaplastic origin. In type 4 adenomyosis \n(KS 4) this was a heterogeneous group where the adenomyosis was \nso “widely extended and expanded that the relationship with uterine \nstructural components could not be clearly evaluated” . The authors \nconclude that this subgroup is a heterogeneous mix of types 1-3 \nadenomyosis (KS 1-3). In their discussion, they draw attention to the \nfact that type 3 adenomyosis (KS 3), was the youngest group of women \n(34 v 38 years), and, to the paradox that some women in each group \nwere symptomatic, though others were asymptomatic.\nThe “Bazot” classification, 2018 (Table 1B)\nBazot recognizes three types of adenomyosis [21]. He draws \nattention to the classification by John Sampson (1921) which he \nreplicates with this MRI classification [19]. He draws distinctions \nbetween what ultrasound examination can do, and, how MR imaging \nadds to the ultrasound observations. Interestingly, Bazot distinguishes \n11 patterns of adenomyosis on MR imaging, most are recognizable \nvariations of his three main groups (BZ 1-3) but two relate to adjacent \ninjuries to the subserosal uterine plexus, and, bladder or rectum. These \nimply significant intrapartum injuries to adjacent organs though these \nare not discussed in detail.\nThe \"Shanghai system\" of classification (Table 2)\nFor a variety of reasons, we offer a third classification of adenomyosis \nbased on clinical, laparoscopic, histologic and radiologic appearances \nthat define the clinical anatomy and histologic injuries carefully (SS \ntypes 1-4, AM; Table 2). \n(a) we noticed clear differences in incidence of some patterns of \nadenomyosis in China compared to Europe.\n(b) we observed some unusual neurologic injuries to the uterine nerve \nsupply in different patterns of adenomyosis \n(c) we noted limited awareness of the nerve supply of the uterus, and, \ndifferent lesions of adenomyosis appears to “map” very precisely to \nthe anatomic sites of the two key, uterine nerve plexi (endometrial-\nmyometrial interface and subserosa)\n(d) in this classification there are four types of adenomyosis (SS, \ntypes 1-4, AM) with types 1-3 associated with precise neurologic \ninjuries.\nType 1 AM, Diffuse, symmetric, painless adenomyosis \n(SS type 1, AM Figure 2A-F)\nIn our initial series of 34/34 women with diffuse, symmetric, \npainless adenomyosis, these women had no uterosacral ligaments \n(P<0.001), no nerves at the endometrial-myometrial nerve plexus \n(P<0.001), and, no nerves in their uteri or Fallopian tubes (P<0.001) \ncompared to controls [2]. Either the injury to uterotubal nerves came \nfirst, or, the enlargement of the uterus destroyed the nerves during the \nenlarging process. We prefer the former explanation since:\n(a) all these women had, at least one, second trimester abortion, \n(which can avulse both uterosacral ligaments in nulliparous \nwomen) \n(b) there are no nerves of any kind at the endometrial-myometrial \nnerve plexus which is continuous with the nerves in the uterosacral \nligaments \n(c) all uteri in this series had similar histology of uterus, uterosacral \nligaments and Fallopian tubes, and weighed between 260g and \n1160g, \n(d) no woman complained of pain; the worst symptoms being \n“heaviness” with “pressure” on bladder and bowel leading to \nfrequency passing urine, and, constipation.\nWe believe this pattern of adenomyosis results from complete loss \nof the nerve supply at the endometrial-myometrial interface owing \nto significant tractino being applied to the cervix (and uterosacral \nligaments) during second trimester abortions that results in complete \navulsions of the uterosacral ligaments. Second trimester abortions are \nrelatively common in China, though unusual in UK clinical practice \nwhere most procedures take place during the first trimester of \npregnancy, often using medical treatment.\nType 2 AM, asymmetric, painful adenomyosis (SS type \n2, AM; Figure 2A-F)\nIn this second pattern of adenomyosis, there is aberrant \nreinnervation in the myometrium in association with asymmetric, \npainful, adenomyosis associated with the endometrial-myometrial \ninterface (SS 2, type 2 adenomyosis, Figure 2A-F). These often occur \nin association with collateral sprouting of nerve bundles that is \npathognomonic of prior traumatic injury (Figure 2C-D). In many cases \nwe find evidence of over-vigorous uterine curettage, difficult vaginal \ndelivery, or, excessive uterine activity associated with administration of \noxytocin, prostaglandins or misoprostol – drugs that were not available \nto TS Cullen in 1908 or JR Sampson in 1921. The injury is largely \nconfined to the body of the uterus and the clinical presentation often \nincludes irregular, painful bleeding at reduced uterine weights (80-\n150g) that regularly results in hysterectomy.\nThere are two patterns of neural injury caused by, at least, two \ndifferent patterns of trauma, in type 2, AM. Firstly, there is a degree \n\nLin Na Z (2019) Neuro-etiologic classification of adenomyosis: the “Shanghai system”\nClin Obstet Gynecol Reprod Med, 2019        doi: 10.15761/COGRM.1000260\n Volume 5: 4-6\n1. Intrinsic adenomyosis that develops in direct connection with a thickened junctional zone (JZ) (KS, type 1, AM)\n2. Extrinsic adenomyosis that develops in the outer shell of the myometrium and the junctional zone was intact (KS, type 2, AM)\n3. Intramural adenomyosis which develops without relationship to the JZ or the subserosal layers (KS, type 3, AM)\n4. Indeterminate adenomyosis that develops outside of the three prior subtypes (KS type 4, AM)\nTable 1A. The “Kishi” classification of adenomyosis.  It is based on stepwise, logistic regression analysis of 152, surgically-treated cases of adenomyosis and published as Kishi Y , \nSuginami H, Kuramori R et al. “Four subtypes of adenomyosis assessed by magnetic resonance imaging and their specification.” Am J Obstet Gynecol 2012; 207: 114 e1-7\n1. Internal adenomyosis (BZ, type 1, AM)\nDiffuse, symmetric or asymmetric widening of myometrium secondary to myometrial hypertrophy with thickening of the junctional zone, often with concurrent leiomyomas\n2. External adenomyosis (BZ, type 2, AM)\nArises in the outer part of the uterus disrupting the subserosa but not affecting the JZ, often associated with “deep” endometriosis.  It can be found with internal adenomyosis or \nadenomyomas.\n3. Adenomyomas (BZ, type 3, AM)\nAn adenomyoma is an ill-defined, myometrial mass containing high-intensity, central cystic areas.  Neither JZ or subserosa are affected by the presence of isolated adenomyoma\nTable 1B. The “Bazot” classification of adenomyosis.  It is based on a descriptive evaluation of transvaginal sonography and magnetic resonance imaging descriptions of adenomyosis \nresulted in three categories of adenomyosis with eleven anatomic, MRI descriptions, published as M. Bazot, E Darai.  “Role of transvaginal sonography and magnetic resoanance imaging \nin the diagnosis of uterine adenomyosis” Fertil Steril 2018; 109(3) 389-397\nType 1 Diffuse, symmetric, painless adenomyosis (SS, type 1, AM; Figure 2)\nThis pattern of adenomyosis typically presents as a painless pelvic mass in a parous woman in her mid-forties with a prior history of one, or more, previous first or second trimester \nabortions.  At laparoscopy there is no evidence of uterosacral ligaments.  Histologically there are no nerves in the uterus or Fallopian tubes, particularly there are no nerves at the site of the \nendometrial-myometrial nerve plexus (JZ).  MR imaging shows symmetrical enlargement of the uterus, with accompanying enlargement of the cervix.\nType 2 Irregular, asymmetric, painful adenomyosis (SS, type 2, AM; Figure 3)\nThis pattern of adenomyosis typically presents with heavy painful, menstrual bleeding in a parous woman in her fifth decade.  Typically, there is evidence of injuries to the uterosacral \nligaments with scarring of their uterine insertions.  Histologically there is aberrant reinnervation in the body of the uterus associated with the endometrial-myometrial interface (JZ). MR \nimaging shows an irregular, asymmetric pattern of adenomyosis centred on the endometrial-myometrial interface.  The uterine cervix may be enlarged owing to accompanying injuries to \nits nerve supply.\nType 3 Focal painless adenomyoma (SS type 3, AM; Figure 4)\nThis pattern of adenomyosis is typically asymptomatic unless associated with other forms of “endometriosis”.  Typically, its “maps” to the two main nerve plexi in the uteri i.e. the \nendometrial-myometrial nerve plexus, or, the subserosal nerve plexus, or, their myometrial branches.  MR imaging shows a focal, high signal intensity, “adenomyoma”.  The uterine cervix \nis usually not enlarged as there has been no injury to its nerve supply.  These adenomyomas can be very large and appear irregular because they are “compressed” between intact, subserosal \nand endometrial-myometrial nerve plexi.\nType 4 Painless intraligamentary adenomyosis (SS type 4, AM)\nThere are a group of other sources of adenomyosis – some are of embryological origin, others are pedunculated, others form atypical adenomyomatoid polyps, that require a separate \ncategory.  They are rare, and, usually distinguishable from more traditional patterns of adenomyosis.\nTable 2. The \"Shanghai system\" of classification of adenomyosis.  This system relies on clinical, laparoscopic, histologic and radiologic features of adenomyosis to produce a neuro-\naetiologic classification.  Each pattern of adenomyosis arises from an injury to the uterine supply that varies with the site, nature and extent of the injury; (A) complete avulsion of \nthe uterosacral ligaments leads to diffuse, symmetric, painless adenomyosis (type 1), (B) excessive traction to the cervix (less than that necessary to produce avulsion) combined with \novervigorous curettage of the endometrium, or, excessive uterine activity, leads to irregular, asymmetric, painful adenomyosis (type 2, AM), (C) partial, pre-uterine injury to a few nerves in \neither uterosacral ligament leads to endometrial or myometrial hyperplasia and development of focal, painless, myoma\nof traction to the cervix that is not sufficient to completely avulse \nthe uterosacral ligaments, but, allows them to reattach to the lower \nuterus and cervix as scarring (Figure 2B) that enables a “bridge” \nfor reinnervation of the lower uterus (Figure 2D). Over-vigorous \ncurettage at the same procedure causes a direct injury to the \nendometrial-myometrial interface creating aberrant reinnervation at \nthe endometrial-myometrial interface (Figure 2C) with subsequent, \nmarked dysmenorrhea that often necessitates an early hysterectomy \nat low uterine weights (80-150g) [3]. Both of these specific injuries \nmay also result from trauma during vaginal delivery; typically uterine \ntachsystole replicates the partial injury to the endometrial-myometrial \ninterface whereas big babies (>4000g), malpresentations, and, operative \nvaginal deliveries may all contribute to injuries to the insertions of the \nuterosacral ligaments and their, contained uterotubal nerves [22].\nType 3 AM, painful or painless, adenomyomas, (SS type \n3, AM; Figure 3A-F)\nIn the third pattern of adenomyosis, there is a circumscribed \ntumor that often “maps” to either the anatomic position of the \nendometrial-myometrial or subserosal nerve plexi, or, most commonly \nthe posterosuperior myometrium of the uterus. Histologically, there is \nloss of nerve fibers in myometrial nerve bundles adjacent to painless \nadenomyomas and leiomyomas (SS 3, Type 3 AM), often with large \nnumbers of narrowed arterioles adjacent to the tumor. We believe \nthese tumors arise from pre-uterine neural injuries because there is no \nevidence of collateral sprouting in these nerve bundles implying that a \nfocal, pre-uterine injury to the nerve bundle had taken place resulting \nin loss of specific, nerve fibers (Figure 3C-D). Sometimes it is possible \nto discern an injury to the uterosacral ligament, or, there is a deposit of \nectopic endometrium to mark the underlying injury (Figure 3B).\nThis injury takes place as part of a first trimester abortion \nprocedure when paracervical infiltration of local anesthesia creates \nthe conditions for injuries to individual nerve fibers, particularly those \nin the superior quadrants of paracervical tissue. Injuries to individual \nnerve fibers in the uterosacral ligaments create neurologic deficits in \nthe myometrium leading to focal hyperplasia, and, formation of an \nadenomyoma or leiomyoma. We do not understand the difference \nbetween the etiology of the two tumors as yet?\nType 4, painless, intraligamentary adenomyoma (SS \ntype 4, AM)\nTS Cullen was aware of this least common pattern of adenomyosis \nthough we are aware there are also adenomyomatous patterns of uterine \npolyp, and, pedunculated forms of adenomyosis that appear to have a \nnon-neurologic origin.\n\nLin Na Z (2019) Neuro-etiologic classification of adenomyosis: the “Shanghai system”\nClin Obstet Gynecol Reprod Med, 2019        doi: 10.15761/COGRM.1000260\n Volume 5: 5-6\nplexus that enters the uterus with the uterine artery [6,17]. Leyendecker \nhas been a proponent of the importance of prior tissue injury in the \n“endometriosis-adenomyosis” spectrum and has emphasized his \nobservation of 11 cases of “cornual” adenomyotic cysts as a rare but \ndistinctive form of adenomyosis [23,24]. In the “Shanghai system” , these \nresult from an unusual injury to the uterine nerve supply at the anterior \nborder of the uterosacral ligament (SS, type 3, AM; Figure 2B). In this \naccount, these injuries to the anterior border of the uteosacral ligament \nare likely to result from paracervical infiltration with lignocaine \nfollowed by traction to the cervix, that contributes to focal tearing of \npre-uterine, nerve fibers with subsequent development of a myoma. \nThere may be other reasons.\nThe increased frequency of the diffuse, symmetric, “painless” \npattern of adenomyosis in China raises a number of important aetiologic \nquestions. Firstly, it appears that 1000g of “ectopic” endometrium can \noccupy a woman’s pelvis without any discomfort to her. Secondly, \nexcessive traction to the cervix during any gynecologic procedure may \navulse one, or more, nerve bundles creating the conditions for all three \ntypes of adenomyosis (SS, types 1-3, AM). Thirdly, the apparent absence \nof SS, type 2, AM in the Cullen and Sampson classifications raises the \nconcern that the injury to the endometrial-myometrial interface, or, \n“junctional zone” is often a contemporary, iatrogenic injury associated \nwith uterotonic agents such as oxytocin, prostaglandins or misoprostol, \nleading to injury to the endometrial-myometrial nerve plexus [1,19]. \nSome patterns of adenomyosis may be preventable by improved \nmanagement of labour, and, evacuation of the uterus. Active measures \nto prevent excessive uterine activity with oxytocin, prostaglandins and \nmisoprostol need more emphasis. There is no reason for excessive \ntraction to the cervix if the surgeon understands there are large numbers \nof delicate nerve bundles associated with its posterior surface. \nAll three, benign, gynecologic pathologies (endometriosis, \nadenomyosis, leiomyoma) carry injuries to the uterine nerve supply [26-\n32]. In this classification we propose that three patterns of adenomyosis \nFigure 4(A-D).  Patterns of injury to the uterosacral ligaments in different patterns of \nadenomyosis. (A) Normal uterosacral ligaments with peritoneal window associated with \nright, uterosacral ligament have nerves running through them that converge on the cervix. \n(B) Bilateral avulsions of uterosacral ligaments cause diffuse, symmetric adenomyosis (SS, \ntype 1, AM, Fig. 1a-f). (C) Bilateral scarring of uterosacral ligaments at uterine insertions & \nover-vigorous curettage of the endometrial cavity cause irregular painful, adenomyosis (SS, \ntype 2, AM, Fig. 2a-f). (D) Discrete injuries to the nerves running through the uterosacral \nligaments associated with paracervical infiltration of anesthetic agents result in focal, \npainless adenomyoma (SS, type 3, AM, Fig 3a-f).\nFigure 3(A-F).  Type 3, focal, painless adenomyoma. (A) Small, (1-2 cm diameter) \nleiomyoma does not compress adjacent histologic features. (B) Focal injury, marked by \nectopic endometrium, at anterior border of uterosacral ligament. (C) Loss of nerve fibers \nin a myometrial nerve bundle beneath the myoma (LS, anti-S100, x100). (D) Loss of nerve \nfibers in a myometrial nerve bundle beneath the myoma (TS, anti-S100, x100). (E) Focal, \nlow intensity signal of a myoma on posterior wall of uterus (T2 weighted, MR scan, LS). \n(F) Focal, low intensity signal of a myoma on posterior wall of uterus (T2 weighted, MR \nscan, TS)\nDiscussion\nThe “Shanghai system” of classification puts together clinical, \nlaparoscopic, histologic and radiologic features to produce explanations \nfor three of the four types of adenomyosis. This appears to be a robust \nsystem given that we have looked at 25-40 cases of each type of \nadenomyosis – some prospectively, some retrospectively – to form this \nclassification. It also appears to “map” to specific injuries to uterotubal \nnerves in, and around, the insertion of the uterosacral ligaments (and \nthe endometrial-myometrial interface) caused by specific clinical \nprocedures with geographical variations in incidence between Eastern \nand Western clinical practice. In that respect it has similarities to the \n“trauma” hypothesis to explain the effects of over-vigorous curettage \nin pregnant rabbits [3], though we extend that hypothesis to include \nsubtle, and less subtle, injuries to the uterosacral ligaments at different \nanatomic sites (Figure 4).\nThe radiologic classifications discussed in this account, are broadly \nsimilar to the “Shanghai system” though vary because they do not \ninclude reference to injuries to uterine nerves. Both Kishi and Bazot’s \nclassifications [20, 22] “map” to the neuroanatomy of the uterus \nwithout either author openly identifying the relationship to the two \nimportant nerve plexi [6,17]. The two key, neurologic plexi being the \nnerve plexus at the endometrial-myometrial junction (Krantz’s plexus) \nthat originates in the uterosacral ligaments, and the subserosal nerve \n\nLin Na Z (2019) Neuro-etiologic classification of adenomyosis: the “Shanghai system”\nClin Obstet Gynecol Reprod Med, 2019        doi: 10.15761/COGRM.1000260\n Volume 5: 6-6\nCopyright: ©2019 Lin Na Z. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, \ndistribution, and reproduction in any medium, provided the original author and source are credited.\ncarry different neuro-anatomic injuries based on simple anatomic \nobservations. If the neuro-etiology of adenomyosis and adenomyoma is \nconfirmed then it raises the question as to the origins of “endometriosis” \nin which increasing numbers of authors are finding neural injuries in \nassociation with deposits of ectopic endometrium [32-34]. 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