This common condition describes the presence of endometrial glands in locations outside of the endometrial cavity. These endometrial glands can still respond to the normal hormones which cause the menstrual cycle. Thus, these glands may grow and lead to hemorrhage. The body responds by forming scar tissue around these glands. This scar tissue and bleeding may lead to pain and infertility as it interferes with the normal implantation of the fertilized egg. Not infrequently, pathologists will find an unsuspected focus of endometriosis in the appendix or even in the belly button (umbilicus).
Epidemiology Disease Associations Pathogenesis Laboratory/Radiologic/Other Diagnostic Testing Gross Appearance and Clinical Variants Histopathological Features and Variants Special Stains/
Differential Diagnosis Prognosis Treatment Commonly Used Terms Internet Links
EPIDEMIOLOGY CHARACTERIZATION INCIDENCE
Varies from 1-15% of women in reproductive age
May be found in 50% of teenage patients with dysmenorrhea or chronic pelvic pain
80% are in reproductive age group
<5% are postmenopausal
Upper socioeconomic levels Possible role of estrogens
DISEASE ASSOCIATIONS CHARACTERIZATION AUTOIMMUNE DISORDERS
High rates of autoimmune and endocrine disorders, fibromyalgia, chronic fatigue syndrome and atopic diseases among women with endometriosis: a survey analysis.
Sinaii N, Cleary SD, Ballweg ML, Nieman LK, Stratton P.
Pediatric and Reproductive Endocrinology Branch, National Institute of Child Health and Human Development, NIH, 10 Center Drive, Building 10, Room 9D42, MSC 1583, Bethesda, MD 20892-1583, USA.
Hum Reprod 2002 Oct;17(10):2715-24 Abstract quote
BACKGROUND: Women with endometriosis may also have associated disorders related to autoimmune dysregulation or pain. This study examined whether the prevalence of autoimmune, chronic pain and fatigue and atopic disorders is higher in women with endometriosis than in the general female population.
METHODS AND RESULTS: A cross-sectional survey was conducted in 1998 by the Endometriosis Association of 3680 USA members with surgically diagnosed endometriosis. Almost all responders had pain (99%), and many reported infertility (41%). Compared with published rates in the general USA female population, women with endometriosis had higher rates of hypothyroidism (9.6 versus 1.5%, P < 0.0001), fibromyalgia (5.9 versus 3.4%, P < 0.0001), chronic fatigue syndrome (4.6 versus 0.03%, P < 0.0001), rheumatoid arthritis (1.8 versus 1.2%, P = 0.001), systemic lupus erythematosus (0.8 versus 0.04%, P < 0.0001), Sjogren's syndrome (0.6 versus 0.03%, P < 0.0001) and multiple sclerosis (0.5 versus 0.07%, P < 0.0001), but not hyperthyroidism or diabetes. Allergies and asthma were more common among women with endometriosis alone (61%, P < 0.001 and 12%, P < 0.001 respectively) and highest in those with fibromyalgia or chronic fatigue syndrome (88%, P < 0.001 and 25%, P < 0.001 respectively) than in the USA female population (18%, P < 0.001 and 5%, P < 0.001 respectively).
CONCLUSIONS: Hypothyroidism, fibromyalgia, chronic fatigue syndrome, autoimmune diseases, allergies and asthma are all significantly more common in women with endometriosis than in women in the general USA population.
DEEP VEIN THROMBOSIS
Multifocal polypoid endometriosis presenting as huge pelvic masses causing deep vein thrombosis.
Laird LA, Hoffman JS, Omrani A.
Department of Pathology, New Britain General Hospital, New Britain, Conn 06050, USA.
Arch Pathol Lab Med. 2004 May;128(5):561-4. Abstract quote
We describe a case of multifocal polypoid endometriosis presenting with advanced bulky disease at a variety of pelvic sites. The extent of tumor and clinical features such as vaginal bleeding and pulmonary embolus were suggestive of a malignant process.
Histopathology demonstrated glands that were neither crowded nor complex, with intervening fibromatous stroma that contained occasional endometrial stromal cells. These features were consistent with the newly described condition of polypoid endometriosis. Despite the endometrioid appearance of this tumor, there was florid ciliary cell change.
An association has been suggested between polypoid endometriosis and prior tamoxifen use, although this patient had no history of prior hormone use.
Endometriosis-associated ovarian carcinoma (EAOC): an entity distinct from other ovarian carcinomas as suggested by a nested case-control study.
Erzen M, Rakar S, Klancar B, Syrjanen K.
Department of Obstetrics and Gynecology, University Medical Centre, 1105 Ljubljana, Slovenia.
Gynecol Oncol 2001 Oct;83(1):100-8 Abstract quote
OBJECTIVES: Endometriosis-associated ovarian carcinoma (EAOC) has recently received increasing attention due to its suggested biological behavior, distinctive from those of usual epithelial ovarian cancer. To elucidate some of the controversies on this intriguing entity, a series of patients with EAOC were compared to ovarian carcinoma cases without concomitant endometriosis.
METHODS: To control the confounding effect of age, a nested case-control study was designed, where all 58 EAOC patients (mean age 54.5 +/- 11.5 years) were nested with four perfectly age-matched non-EAOC patients (n = 232; mean age 54.7 +/- 11.7 years) selected among 425 women representing all FIGO stages of ovarian carcinomas without endometriosis. Pertinent clinical data and results of analysis of the tumors were subjected to statistical analyses using life-table, univariate (Kaplan-Meier), and multivariate (Cox) survival techniques to disclose dissimilarities in the key biological characteristics of these two groups as well as the independent prognostic predictors of disease outcome.
RESULTS: When compared in a case-control design with four perfectly age-matched non-EAOC patients nested to each EAOC case, the patients with EAOC proved to: (1) have a lower stage disease (both FIGO and TNM) (P = 0.000), (2) show a completely different distribution of histological subtypes (significant overpresentation of endometrioid and clear cell carcinomas) (P = 0.0001), (3) have predominantly lower grade lesions (P = 0.029), (4) be devoid of any primary residual tumor (P = 0.0001), and, most importantly (5) have demonstrated a significantly better overall survival (47/58 versus 126/232; OR 2.89, 95% CI 1.56-5.34, P = 0.0001). This better survival was evident (a) in all age groups and (b) for all histological subtypes, but (c) not explained by a better stage-specific survival in any FIGO stage. The two series also differed in their significant prognostic predictors in Kaplan-Meier and Cox analyses. In the EAOC group, the most significant (P = 0.0001) predictors of OS in univariate analysis were age, histological type, observation time for endometriosis, and distribution of endometriosis. In the non-EAOC group, such significant predictors were age, residual tumor, and type of therapy. In the multivariate (Cox) model, age and FIGO stage were the only two significant independent prognostic factors shared by these two series. In addition, histological type and type of therapy proved to be significant independent predictors in the non-EAOC series.
CONCLUSIONS: These data suggest that EAOC deviates from the non-EAOC in many of its key biological characteristics. The implications of these data in the diagnosis, treatment policy, and prognostication still require confirmation by further studies, however.
Benign or malignant ovarian neoplasms and ovarian endometriomas.
Takahashi K, Kurioka H, Irikoma M, Ozaki T, Kanasaki H, Miyazaki K.
Department of Obstetrics and Gynecology, Shimane Medical University, 89-1, Enya-cho, Izumo, Shimane 693-8501, Japan.
J Am Assoc Gynecol Laparosc 2001 May;8(2):278-84 Abstract quote
STUDY OBJECTIVE: To investigate clinical features and biologic behavior of ovarian cancer that might be closely related to endometrioma and/or endometriosis.
DESIGN: Retrospective study (Canadian Task Force classification II-2).
SETTING: University hospital.
PATIENTS: All 324 women who were operated for endometriomas and/or ovarian tumors 5 cm or greater in diameter between January 1988 and December 1997.
INTERVENTION: One hundred twelve women underwent laparoscopic surgery and 212 had laparotomy.
MEASUREMENTS AND MAIN RESULTS: All tissues were evaluated histologically. Clinical examinations including ultrasound and serum tumor makers were performed in all patients preoperatively. No malignancies were found at laparoscopic surgery (76 endometriomas, 36 ovarian tumors). The frequency of endometriosis in benign, borderline malignant, and malignant tumors was 9.7%, 12.5%, and 11.4%, respectively. Endometriosis was present most frequently (40%) in women with endometrioid adenocarcinoma. It was present in 81 patients with endometriomas and 25 with ovarian neoplasms. Of these, nine women (8.5%) had malignant tumors, including borderline malignancy. Among patients with malignant tumors, those without endometriosis were significantly older (mean +/- SD age 54.9 +/- 16.2 yrs) than those with endometriosis elsewhere in the pelvis (45.9 +/- 8.9 yrs).
CONCLUSION: Endometriosis may be closely related to ovarian tumors such as endometrioid adenocarcinoma. Surgeons should be aware of this possibility, and candidates for laparoscopic surgery should be carefully selected based on preoperative evaluations.
PATHOGENESIS CHARACTERIZATION General Metastatic theory Metastases of endometrial tissue to an ectopic location Menstrual implantation Intraoperative implantation Lymphatic and vascular spread Metaplastic theory Metaplastic developement of endometrial tissue developing in ectopic locations Genetic factors 4.9% risk for first degree relatives Hormonal factors Estrogen probably important since it occurs almost exclusively in women of reproductive age Immune factors Reduced T-lymphocyte mediated cytotoxicity to autologous endometrial cells
Peritoneal endometriosis: validation of an in-vivo model.
Grummer R, Schwarzer F, Bainczyk K, Hess-Stumpp H, Regidor PA, Schindler AE, Winterhager E.
Institute of Anatomy, University Hospital Essen, 45122 Essen, Germany.
Hum Reprod 2001 Aug;16(8):1736-43 Abstract quote
BACKGROUND: The current medical treatment of endometriosis, a common gynaecological disease, is still associated with a high recurrence rate. To establish an appropriate in-vivo model to evaluate new therapeutic strategies we validated the nude mouse model for the intraperitoneal cultivation of human endometrial tissue.
METHODS: Human endometrium of the proliferative phase was implanted into the peritoneal cavity of normal cycling and ovariectomized athymic mice and of cycling non-obese diabetic (NOD)-severe combined immuno-deficiency (SCID) mice. Morphology, proliferation, differentiation, and angiogenesis in the ectopic endometrium at different time points after implantation was investigated.
RESULTS: Adhesion of endometrial fragments was observed from daJ Clin Lab Anal 2001;15(4):184-7 Related Articles, Books, LinkOut p21 gene codon 31 arginine/serine polymorphism: non-association with endometriosis. Hsieh YY, Tsai FJ, Chang CC, Chen WC, Tsai CH, Tsai HD, Lin CC. Department of Obstetrics and Gynecology, China Medical College Hospital, Taichung, Taiwan. p21, an important regulator of the cell cycle, acts as a mediator of the growth-suppressing and -promoting functions of p53. We aimed to investigate the association between codon 31 polymorphisms of p21 gene and endometriosis. Women were divided into two groups: endometriosis (n = 102) and nonendometriosis (n = 119). The gene polymorphism for p21 codon 31 involved a base change from AGC to AGA and amino acid changes from serine (Ser) to arginine (Arg). Polymorphisms (Ser homozygotes, heterozygotes, Arg homozygotes) between both groups were detected and compared. Associations between the endometriosis and polymorphisms were evaluated. The results revealed that the distributions of different p21 polymorphisms in both groups were nonsignificantly different. The proportions of Ser homozygote/heterozygote/Arg homozygote in endometriosis and nonendometriois populations were 26.5/48.0/25.5% and 17.6/50.4/31.9%, respectively. We concluded the noncorrelation between the endometriosis and the p21 codon 31 polymorphism. p21 gene codon 31 arginine/serine polymorphism is not a useful marker for prediction of endometriosis susceptibility. y 2 onwards. The lesions persisted for up to 28 days revealing a well preserved glandular morphology. The glandular epithelium maintained cytokeratin expression even after 14 days of culture. With progressing culture, glands exhibited vimentin staining in combination with a decrease of surrounding stromal cells. Proliferation of glandular epithelium could be demonstrated throughout the investigated period of 28 days, whereas expression of oestrogen and progesterone receptors was maintained only in endometriotic lesions grown in cycling but not in ovariectomized mice. Neoangiogenesis occurred from day 4 onwards, independent from the intraperitoneal localization of the ectopic lesions.
CONCLUSIONS: This in-vivo model is a promising tool to test the effect of compounds such as different hormone agonists/antagonists or anti-angiogenic factors to develop new therapeutic concepts in endometriosis.
Human arylhydrocarbon receptor repressor (AHRR) gene: genomic structure and analysis of polymorphism in endometriosis.
Watanabe T, Imoto I, Kosugi Y, Fukuda Y, Mimura J, Fujii Y, Isaka K, Takayama M, Sato A, Inazawa J.
Department of Molecular Cytogenetics, Tokyo Medical and Dental University, Japan
J Hum Genet 2001;46(6):342-6 Abstract quote
The diversity of biological effects resulting from exposure to dioxin may reflect the ability of this environmental pollutant to alter gene expression by binding to the arylhydrocarbon receptor (AHR) gene and related genes.
AHR function may be regulated by structural variations in AHR itself, in the AHR repressor (AHRR), in the AHR nuclear translocator (ARNT), or in AHR target molecules such as cytochrome P-4501A1 (CYP1A1) and glutathione S-transferase. Analysis of the genomic organization of AHRR revealed an open reading frame consisting of a 2094-bp mRNA encoded by ten exons. We found one novel polymorphism, a substitution of Ala by Pro at codon 185 (GCC to CCC), in exon 5 of the AHRR gene; among 108 healthy unrelated Japanese women, genotypes Ala/Ala, Ala/Pro, and Pro/Pro were represented, respectively, by 20 (18.5%), 49 (45.4%), and 39 (36.1%) individuals. We did not detect previously published polymorphisms of ARNT (D511N) or the CYP1A1 promoter (G-469A and C-459T) in our subjects, suggesting that these polymorphisms are rare in the Japanese population.
No association was found between uterine endometriosis and any polymorphisms in the AHRR, AHR, ARNT, or CYP1A1 genes analyzed in the present study.
Genetic alterations in microsatellite marker sites among tumor suppressor genes in endometriosis.
Nakayama K, Toki T, Nikaido T, Zhai YL, Konishi I.
Department of Obstetrics and Gynecology, Shinshu University School of Medicine, Matsumoto, Japan
Gynecol Obstet Invest 2001;51(4):240-2 Abstract quote
Four endometriotic lesions were examined for the presence of genetic alterations in microsatellite marker sites among eight tumor suppressor genes. For this, a microdissection method was used on paraffin sections. Only one instance of loss of heterozygosity was detected at the PTCH locus. Heterozygosity was retained (indicating the absence of both loss of heterozygosity and microsatellite instability) at the other seven tumor suppressor gene loci in all the cases. Among the tumor suppressor genes examined, genetic defects in these microsatellite regions are certainly not ubiquitous in endometriosis and may be uncommon.
The genetic basis of endometriosis.
Zondervan KT, Cardon LR, Kennedy SH.
Wellcome Trust Centre for Human Genetics, Oxford, UK.
Curr Opin Obstet Gynecol 2001 Jun;13(3):309-14 Abstract quote
Family studies have long suggested a role for genetic factors in the aetiology of endometriosis. The influence of genes on disease development has mainly been researched independently of environmental factors, yet their interaction must play an important role. Greater exposure to retrograde menstruation and oestrogen is likely to increase the risk of endometriosis; toxic compounds such as dioxin may increase the risk, although the only direct evidence has come from primate studies.
Previous association studies implicated GALT (a gene involved in galactose metabolism), and GSTM1 and NAT2 (genes encoding for the detoxification enzymes) as possible disease susceptibility genes. Recent findings have added to the evidence for the involvement of GSTM1 and NAT2, but have cast doubt on the role of GALT. However, the design of many genetic and epidemiological studies has been inadequate with respect to sample size, consistency in phenotype definition, and the choice of control populations.
These features are likely to influence results, and could partly explain the lack of consistency in the findings. Future studies should use a consistent disease definition and be of appropriate epidemiological design.
INTEGRINS Immunohistochemical Analysis of v5 and v6 Integrins in the Endometrium and Endometriosis
Libertad A. Puy, M.D.; Carol Pang, M.D.; Clifford L. Librach, M.D.
From the Toronto Hospital Research Institute (L.P.), and Sunnybrook & Women's College Health Sciences Centre (C.P., C.L.), Department of Obstetrics and Gynecology, University of Toronto, Ontario, Canada.
Int J Gynecol Pathol 2002;21:167-177 Abstract quote
We performed a case-controlled study to study the immunoreactivity patterns and staining intensity of v5 and v6 integrins in ectopic and eutopic endometrium from women with endometriosis and compared them with those in normal control endometrium.
Forty eutopic and ectopic samples from patients with endometriosis were compared with 12 control endometrial samples. Staining was evaluated using a computerized image analysis system by a blinded, independent observer. The immunoreactivity patterns for both v5 and v6 were very similar. In eutopic endometrium from women with or without endometriosis, the immunostaining intensity score for both integrins was stronger during the secretory than the proliferative phase. Immunoreactivity in endometriosis was greater than in eutopic endometrium. There were no significant menstrual cycle-related staining differences in endometriosis. The percentage of blood vessels immunolabeled was greater in endometriosis than eutopic endometrium from endometriosis patients and greater in eutopic endometrium from these patients compared with control endometrium. Ectopic tissue from patients with stages I and II endometriosis showed significantly higher staining intensity than ectopic tissue from patients with stages III and IV disease.
Determination of the specific functional consequences of the differences observed in v5 and v6 integrin immunostaining may provide an increased understanding regarding the pathogenesis of endometriosis.
p21 gene codon 31 arginine/serine polymorphism: non-association with endometriosis.
Hsieh YY, Tsai FJ, Chang CC, Chen WC, Tsai CH, Tsai HD, Lin CC.
Department of Obstetrics and Gynecology, China Medical College Hospital, Taichung, Taiwan.
J Clin Lab Anal 2001;15(4):184-7 Abstract quote
p21, an important regulator of the cell cycle, acts as a mediator of the growth-suppressing and -promoting functions of p53.
We aimed to investigate the association between codon 31 polymorphisms of p21 gene and endometriosis. Women were divided into two groups: endometriosis (n = 102) and nonendometriosis (n = 119). The gene polymorphism for p21 codon 31 involved a base change from AGC to AGA and amino acid changes from serine (Ser) to arginine (Arg). Polymorphisms (Ser homozygotes, heterozygotes, Arg homozygotes) between both groups were detected and compared. Associations between the endometriosis and polymorphisms were evaluated. The results revealed that the distributions of different p21 polymorphisms in both groups were nonsignificantly different. The proportions of Ser homozygote/heterozygote/Arg homozygote in endometriosis and nonendometriois populations were 26.5/48.0/25.5% and 17.6/50.4/31.9%, respectively.
We concluded the noncorrelation between the endometriosis and the p21 codon 31 polymorphism. p21 gene codon 31 arginine/serine polymorphism is not a useful marker for prediction of endometriosis susceptibility.
Immunohistochemical assessment of superoxide dismutase expression in the endometrium in endometriosis and adenomyosis.
Ota H, Igarashi S, Hatazawa J, Tanaka T.
Department of Obstetrics and Gynecology, Akita University School of Medicine, Akita-city, Japan.
Fertil Steril 1999 Jul;72(1):129-34 Abstract quote
OBJECTIVE: To determine the expression of superoxide dismutase (SOD) in the endometrium during the menstrual cycle in endometriosis and adenomyosis.
DESIGN: Immunohistochemical identification of SOD in endometrial tissues using the monoclonal antibody.
SETTING: Department of obstetrics and gynecology in a university hospital.
PATIENT(S): The subjects were divided into three groups: 36 patients with endometriosis, 38 patients with histologically proven adenomyosis, and 47 fertile control subjects.
INTERVENTION(S): Endometrium was biopsied throughout the menstrual cycle. MAIN
OUTCOME MEASURE(S): Semiquantitative immunostaining (evaluation nomogram) score for endometrial cells.
RESULT(S): The analyses revealed phase-dependent changes in the expression of SODs in the glandular and surface epithelia during the menstrual cycle in fertile controls. Specifically, the expression of copper, zinc SOD was weakest in the early and midproliferative phases, then gradually increased, and was most marked in the early and midsecretory phases. The expression of manganese SOD reached a peak in the late secretory phase. The expression of both SODs in endometriosis and adenomyosis was persistently higher than the control levels throughout the menstrual cycle.
CONCLUSION(S): The exaggerated expression of both SODs in the endometrium throughout the menstrual cycle suggests that superoxide plays a key role in infertility in endometriosis and adenomyosis.
CHARACTERIZATION CA-125 May be elevated in the serum and peritoneal fluid Anti-endometrial antibodies 35-83% of cases CATHEPSIN D
Increased concentrations of cathepsin D in peritoneal fluid from women with endometriosis.
Suzumori N, Ozaki Y, Ogasawara M, Suzumori K.
Department of Obstetrics and Gynecology, Nagoya City University Medical School, Nagoya, Japan.
Mol Hum Reprod 2001 May;7(5):459-62 Abstract quote
To assess the release of the proteolytic enzyme cathepsin D in endometriosis, concentrations in peritoneal fluid and serum were measured by ELISA in 54 women with (n = 33) and without (n = 21) endometriosis. Surgery was scheduled in either the proliferative or secretory phase of the menstrual cycle. The concentrations of cathepsin D in the peritoneal fluid were markedly elevated in the endometriosis patients (median 58 ng/ml, interquartile range 0-166 ng/ml) as compared to the controls (5 ng/ml, 0-86 ng/ml), especially in women with late stage disease (n = 19, stages III/IV) and in those not undergoing gonadotrophin-releasing hormone (GnRH) agonist therapy (n = 15). No significant difference was determined in cathepsin D concentrations of the serum from women with and without endometriosis.
We conclude that cathepsin D is an important factor that may contribute to the pathogenesis of endometriosis, possibly by promoting digestion of extracellular matrix proteins. These results have implications for the therapeutic efficacy of GnRH agonists.
Cytokine profiles in autologous peritoneal fluid and peripheral blood of women with deep and superficial endometriosis.
D'Hooghe TM, Xiao L, Hill JA.
Leuven University Fertility Center, Department of Obstetrics and Gynecology, University Hospital Gasthuisberg, Belgium.
Arch Gynecol Obstet 2001 Mar;265(1):40-4 Abstract quote
In a preliminary study the hypothesis was tested that cytokine profiles in peripheral blood were higher in women with deep infiltrating endometriosis and cytokine profiles in peritoneal fluid were higher in women with superficial endometriosis.
Thirteen women of reproductive age having laparoscopy for infertility (n=9), pain (n=3) or combined pain and infertility (n=1). Peripheral blood and peritoneal fluid were obtained and analyzed for Interleukin-6 (IL-6), Tumor Necrosis Factor-alpha (TNF-alpha), Interleukin-10 (IL-10), Transforming Growth Factor-betal (TGFbeta1), and Interferon-gamma (IFN-gamma). No significant cytokine differences were observed in either peritoneal fluid or peripheral blood between IL-6, TGFbeta1, IFNgamma, TNF-alpha and IL-10 of women with superficial endometriosis (n=7) and women with deeply infiltrating endometriosis (n=6).
The results of this preliminary study do not show significant differences in peripheral blood and peritoneal fluid cytokine levels between women with deep infiltrating endometriosis compared to women with superficial disease. Future studies with increased sample size are required to either confirm or refute these preliminary findings.
Correlation between decreased type-II interleukin-1 receptor and increased monocyte chemotactic protein-1 expression in the endometrium of women with endometriosis.
Kharfi A, Akoum A.
Laboratoire d'Endocrinologie de la Reproduction, H pital Saint-Francois d'Assise Centre, Hospitalier Universitaire de Quebec, Universite Laval, Canada.
Am J Reprod Immunol 2001 Apr;45(4):193-9 Abstract quote
PROBLEM: Monocyte chemotactic protein-1 (MCP-1), a potent inducer of macrophage recruitment and activation, is overexpressed in the eutopic endometrium of women with endometriosis. Eutopic endometrial cells of women with endometriosis secrete higher levels of MCP-1 than those of normal women, following stimulation with interleukin-1 (IL-1). The aim of this study was to examine whether there is any correlation between the expression of IL-1 receptor type II (IL-IRII), a specific downregulator of IL-1 activity, and that of MCP-1 in the eutopic endometrium of women with endometriosis.
METHOD OF STUDY: Endometrial biopsies of 46 women with endometriosis and 22 healthy women were evaluated simultaneously for IL-1RII and MCP-1 expression by immunohistochemistry.
RESULTS: Our study revealed a highly significant correlation between the decreased expression of IL-1RII and the increased expression of MCP-1 in the endometrial tissue of women with endometriosis (Spearman correlation coefficient r = -0.377, P = 0.002), particularly in the initial stages of the disease (stages I and II; r = - 0.368, P = 0.020 and r = -0.480, P = 0.002, respectively). Furthermore, this correlation was observed in the proliferative (r = -0.366, P = 0.047) and the secretory phases (r = -0.321, P = 0.049) of the menstrual cycle.
CONCLUSIONS: These results suggest that the reduced capability of endometrial tissue to downregulate IL-1 proinflammatory effects may be involved in the increased expression of MCP-1 in the endometrium of women with endometriosis and the establishment of an inflammatory state. The results also indicate a sustained process of cell activation throughout the menstrual cycle.
Regulation of matrix metalloproteinases and their inhibitors in uterine endometrial cells of patients with and without endometriosis.
Sillem M, Prifti S, Koch A, Neher M, Jauckus J, Runnebaum B.
Department of Obstetrics and Gynaecology, Division of Gynecological Endocrinology and Reproductive Medicine, Heidelberg, Germany
Eur J Obstet Gynecol Reprod Biol 2001 Apr;95(2):167-74 Abstract quote
OBJECTIVE: To determine whether alterations in the secretion and regulation of matrix metalloproteinases (MMPs) and their inhibitors are present in uterine endometrial cells from endometriosis patients.
STUDY DESIGN: In an in vitro study, uterine endometrial cells from 19 regularly cycling women with and 32 without endometriosis were treated with diethyl stilbestrol, promegestone (R5020), interleukin-1 (IL-1) and tumor necrosis factor a (TNF-alpha). Culture supernatants were assayed for MMPs 1, 2, 3, and 9, and for tissue inhibitors of MMP (TIMP-1 and TIMP-2) by ELISA.
RESULTS: MMP-3 was secreted in high concentrations, moderate concentrations were seen for MMP-1 and MMP-2, and very low concentrations for MMP-9. Substantially more TIMP-1 than TIMP-2 was secreted. MMP-1 and MMP-3 were uniformly attenuated by R5020, while MMP-2 was not influenced by hormone treatment. MMP-3 was upregulated by TNF-alpha in all samples while IL-1 only increased secretion in cells from endometriosis patients.
CONCLUSION: The upregulation of MMP-3 by IL-1 may contribute to an increased invasiveness of uterine endometrial fragments in endometriosis patients.
GROSS APPEARANCE/CLINICAL VARIANTS CHARACTERIZATION GENERAL
Early lesions resemble punctate red, blue, brown, or black powder burns and may be associated with fibrous adhesions
Endometriosis: correlation between histologic and visual findings at laparoscopy.
Walter AJ, Hentz JG, Magtibay PM, Cornella JL, Magrina JF.
Department of Obstetrics and Gynecology and the Section of Biostatistics, Mayo Clinic Scottsdale, Arizona, USA.
Am J Obstet Gynecol 2001 Jun;184(7):1407-11 Abstract quote
OBJECTIVE: The purpose of this study was to correlate the diagnosis of endometriosis on the basis of visualization at laparoscopy with the pathologic diagnosis.
STUDY DESIGN: A prospective study of 44 patients undergoing laparoscopy for the evaluation of chronic pelvic pain was carried out. All areas suggestive of endometriosis were excised and examined pathologically. Peritoneal biopsy specimens were obtained from areas of normal-appearing peritoneum to rule out microscopic endometriosis. All lesions were identified by anatomic site. Visual and histologic American Fertility Society scores were compared. The positive predictive value, sensitivity, negative predictive value, and specificity were determined for visually identified endometriosis versus the histologic correlate.
RESULTS: The mean prevalence of abnormalities visually consistent with endometriosis was 36%, with 18% confirmed histologically. The positive predictive value was 45%; sensitivity, 97%; negative predictive value, 99%; and specificity, 77%; for visual versus histologic diagnosis of endometriosis. Thirty-six percent of the diagnoses were downstaged on the basis of histologic findings.
CONCLUSION: A diagnosis of endometriosis should be established only after histologic confirmation.
Chocolate cysts of the ovary Endometriotic cysts may involve the ovary Cervical and vaginal
2.4-15% of cases
Usually involve areas of prior trauma, site of prior cone biopsy, or extensive cautery
Deep cervical lesions usually result from extension of cul-de-sac involvement
Tubal May extend around the surface, occlude the lumen (intraluminal endometriosis), or involve the tip of the proximal tubal stump of a tubal ligation Intestinal 37% of patients undergoing laparotomy
Usually confined to the serosa or subserosa
Endometriosis of the Intestinal Tract A Study of 44 Cases of a Disease That May Cause Diverse Challenges in Clinical and Pathologic Evaluation
Rhonda K. Yantiss, etal.
Am J Surg Pathol 2001;25:445-454 Abstract quote
Endometriosis of the intestinal tract may mimic a number of diseases both clinically and pathologically. The authors evaluated 44 cases of intestinal endometriosis in which endometriosis was the primary pathologic diagnosis, and evaluated them for a variety of gross and histologic changes. Cases with preneoplastic or neoplastic changes were excluded specifically because they were the subject of a previous study.
The patients ranged in age from 28 to 56 years (mean age, 44 years), and presenting complaints included abdominal pain (n = 15), an abdominal mass (n = 12), obstruction (n = 8), rectal bleeding (n = 2), infertility (n = 3), diarrhea (n = 2), and increasing urinary frequency (n = 1). The clinical differential diagnoses included diverticulitis, appendicitis, Crohn's disease, tubo-ovarian abscess, irritable bowel syndrome, carcinoma, and lymphoma. Forty-two patients underwent resection of the diseased intestine and two patients underwent endoscopic biopsies. In 13 patients there were predominantly mural masses, which were multiple in two patients (mean size, 2.6 cm). In addition, 11 cases had luminal stenosis or strictures, six had mucosal polyps, four had submucosal masses that ulcerated the mucosa (sometimes simulating carcinoma), three had serosal adhesions, one had deep fissures in the mucosa, and one was associated with appendiceal intussusception. Involvement of the lamina propria or submucosa was identified in 29 cases (66%) and, of these, 19 had features of chronic injury including architectural distortion (n = 19), dense lymphoplasmacytic infiltrates (n = 7), pyloric metaplasia of the ileum (n = 1), and fissures (n = 1). Three cases had features of mucosal prolapse (7%), ischemic changes were seen in four (9%), and segmental acute colitis and ulceration were seen in four and six cases (9% and 13%) respectively. In 14 patients, endometriosis formed irregular congeries of glands involving the intestinal surface epithelium, mimicking adenomatous changes. Mural changes included marked concentric smooth muscle hyperplasia and hypertrophy, neuronal hypertrophy and hyperplasia, and fibrosis of the muscularis propria with serositis. Follow-up of 20 patients (range, 1–30 years; mean, 7.8 years) revealed that only two patients had recurrent symptoms. None of the patients developed inflammatory bowel disease.
Endometriosis can involve the intestinal tract extensively, causing a variety of clinical symptoms, and can result in a spectrum of mucosal alterations. Because the endometriotic foci may be inaccessible to endoscopic biopsy or may not be sampled because of their focality, clinicians and pathologists should be aware of the potential of this condition to mimic other intestinal diseases.
Urinary tract 16-20% of cases
Usually on serosa of the urinary bladder or ureters
Inguinal In 1/3 of cases may be associated with an inguinal hernia Lymph nodes 12% of patients who had lymph nodes examined in cases of pelvic endometriosis Pleuropulmonary
Pleural cases present with repeated episodes bloody pneumothorax, usually right sided
Lung parenchymal cases present with hemoptysis
Thoracic endometriosis syndrome resembling pulmonary embolism.
Rychlik DF, Bieber EJ.
Department of Obstetrics and Gynecology (M/C 2050), Division of Reproductive Endocrinology, University of Chicago, MARP-303, Chicago, IL 60637, USA.
J Am Assoc Gynecol Laparosc 2001 Aug;8(3):445-8 Abstract quote
A 32-year-old infertility patient with a previous diagnosis of stage IV endometriosis experienced shortness of breath and chest pain.
She was diagnosed with a pulmonary embolism by spiral volumetric computed tomography (SVCT) and anticoagulated during hospitalization, although no history of thrombosis was ever identified. She continued to have intermittent symptoms of chest pain, back pain, and shortness of breath for the next 1.5 months. Repeat SVCT revealed a large, right-sided pleural effusion with associated consolidation but no evidence of pulmonary embolism. To obtain a definitive diagnosis, a thoracoscopic pleural biopsy was performed and showed thoracic endometriosis involving the pleura. The patient desired to retain her fertility and opted for treatment with depot medroxyprogesterone. She has been asymptomatic for 2 years with this treatment.
This case illustrates the importance of recognizing thoracic endometriosis syndrome and the difficulty diagnosing this condition considering its nonspecific features.
Soft tissue and skeletal Sites have included trapezius, biceps femoris, thigh, knee, and thumb Upper abdomen May occur on omentum, liver surface, or diaphragm Nervous system Involve the sciatic nerve sheath at the level of the sciatic notch
Rare case of subarachnoid deposits
Men Rarely occurs in men receiving long-term estrogen therapy for prostate cancer SKIN Most cases occur in surgical scars, average postoperative interval is about 30 months
- Morphological variations of scar-related and spontaneous endometriosis of the skin and superficial soft tissue: a study of 71 cases with emphasis on atypical features and types of müllerian differentiations.
Sikl's Department of Pathology, Charles University Medical Faculty Hospital, Pilsen, Czech Republic.
- J Am Acad Dermatol. 2007 Jul;57(1):134-46. Abstract quote
BACKGROUND: Seventy-one cases of scar-related and spontaneous endometriosis of the skin and superficial soft tissue were studied, with a focus on atypical features and types of müllerian differentiation. All patients were women, whose ages ranged from 22 to 65 years (median, 32 years).
METHODS: Histological, immunohistochemical, and electronmicroscopic studies were performed. Clinical information was ascertained via a questionnaire solicited by the referring physicians.
RESULTS: All types of metaplastic changes of müllerian epithelium were found, including tubal (61%), oxyphilic (15%), hobnail (10%), mucinous (4%), and papillary syncytial (3%) metaplasia. Atypical features included reactive atypia (23%) and atypical mitoses in glandular epithelium (6%). Stromal changes included smooth muscle metaplasia (31%), decidualization (<1%), stromal endometriosis (<1%), and elastosis (<1%). Other features recognized included lipoblast-like cells (15%), some with intranuclear inclusions; atypical/degenerative myocytes (10%); spiral arteries (4%); and perineurial invasion (<1%). CD56 staining identified large granular lymphocytes in 15 of 20 studied specimens. Ultrastructurally, these cells showed cytoplasmic granules, some with a delimiting membrane.
LIMITATIONS: This study utilizes tissue specimens that mainly were received as consultations; therefore some inherent selection bias exists. Specimens were randomly selected for CD56 immunostaining, leading also to potential sampling error.
CONCLUSIONS: All types of müllerian metaplasia can be encountered in cutaneous endometriosis. In addition, so-called atypical features described in endometriosis affecting other anatomic sites may be seen in the skin. Some features may represent a diagnostic pitfall.
HISTOLOGICAL TYPES CHARACTERIZATION GENERAL Endometrial glands in stroma-these glands my exhibit cyclic changes with the hormonal cycle in 44-80% of cases
Pathogenetic role of the stromal cells in endometriosis and adenomyosis.
Mai KT, Yazdi HM, Perkins DG, Parks W.
Department of Laboratory Medicine, Ottawa Civic Hospital, Ontario, Canada.
Histopathology 1997 May;30(5):430-42 Abstract quote
Ten cases of endometriosis of bowel, ovaries, uterine serosa and 10 cases of adenomyosis were studied.
Blocks of tissue with areas of interest were submitted for serial sectioning of the entire block. Some sections were immunostained for oestrogen receptor, vimentin, Ber-EP-4 and cytokeratins. The common finding was the presence of type 1 nodules, consisting of isolated nodules of endometrial stromal cells without endometrial glands, along blood or lymphatic vessels. The stromal cells showed positive immunoreactivities for oestrogen receptor and vimentin, and negative reactivities for cytokeratins. Due to the absence of connection with adjacent endometriosis or adenomyosis, it is likely that these endometrial stromal nodules arise from the multipotential pericytes. In addition, in serosa of all cases of endometriosis, type 2 nodules, having adjacent mesothelium (Ber-EP4-) changing into epithelium (Ber-EP4+) and type 3 nodules, with non-endometrial epithelium (oestrogen receptor-) changing into endometrial gland (oestrogen receptor+) were identified. We believe that the formation of type 1 nodules from the pericytes and the transformation of the mesothelium into endometrial glands in type 2 and 3 nodules are accomplished through the process of induction by the endometrial stroma, and the proliferation is controlled by genetic, hormonal and immunological factors.
Type 1, 2 and 3 nodules are likely to represent a histological continuum in the development of early endometriosis. Subsequent to the formation of endometriosis in the serosa, the pathway of development of endometriosis and adenomyosis is similar. Through the processes of induction and proliferation there is an increase in size of the stroma of type 1 nodules and that of endometrial tissue with subsequent fusion of the stroma of type 1 nodules and that of foci of adenomyosis or endometriosis. Consequently, there is enlargement of the stroma of the foci of adenomyosis or endometriosis. The 'newly enlarged stroma' serves as 'new soil' for further growth of the endometrial glands in the endometrial tissue.
CYSTIC Endometrial lining may be attenuated or lost and replaced with granulation tissue, dense fibrous tissue, and pseudoxanthoma cells
Classification of ovarian endometriotic cysts.
Scurry J, Whitehead J, Healey M.
Department of Pathology, Mercy Hospital for Women, Clarendon Street, East Melbourne, Vic. 3002, Australia.
Int J Gynecol Pathol 2001 Apr;20(2):147-54 Abstract quote
Current literature describes 3 different pathogenetic types of ovarian endometriotic cysts.
Cortical invagination cysts arise when surface ovarian endometriotic deposits adhere to another structure (such as the broad ligament), blocking the egress of menstrual fluid produced by cycling endometriosis, which then collects and causes the ovarian cortex to invaginate. Surface inclusion cyst-related endometriotic cysts develop when endometriotic tissue colonizes preexisting inclusion cysts. Physiological cyst-related endometriotic cysts occur when endometriosis gains access to a follicle, such as at the time of ovulation. To determine whether routine histological examination is of use in the classification of endometriotic cysts, and if so, whether such classification is of clinical relevance, we reviewed the histology of endometriotic cysts of 29 women under 35 years of age. Young women were chosen so that ovarian cortex surrounding the endometriotic lining in invagination cysts could be identified by the finding of oocytes. Ten women (34%) had cortical invagination endometriotic cysts, but no inclusion or physiological cyst-related endometriomas were found. The remaining 19 women (66%) had unclassified endometriotic cysts, of which 14 (48% of total) had a fibrous wall between the endometriotic lining and medulla and 5 had extensive destruction of ovarian tissue.
We concluded that cortical invagination cysts were the only common diagnosable sort of the 3 types currently being investigated and that unclassified cysts required further study to determine their pathogenesis. Our study highlights the need for a prospective study using standardized pathological and clinical methods.
EPITHELIAL ATYPIA May occur and may be a risk factor for development of carcinoma
Neoplastic and Pre-Neoplastic Changes in Gastrointestinal Endometriosis A Study of 17 Cases
Rhonda K. Yantiss, M.D.; Philip B. Clement, M.D.; Robert H. Young, M.D.
From the Department of Pathology, Harvard Medical School, and the James Homer Wright Pathology Laboratories of the Massachusetts General Hospital, Boston, Massachusetts (R.K.Y., R.H.Y.), and the Department of Pathology, University of British Columbia and the Department of Pathology, Vancouver General Hospital, Vancouver, British Columbia (P.B.C.).
Am J Surg Pathol 2000;24:513-524 Abstract quote
The clinicopathologic features of neoplasms arising in gastrointestinal endometriosis have not been well characterized.
In this series, we report 17 cases of gastrointestinal endometriosis complicated by neoplasms (14 cases) or precancerous changes (three cases). Four patients, one of whom also had hypermenorrhea, presented with chronic abdominal pain and five had obstructive symptoms; one of these also had rectal bleeding. One patient presented with an acute abdomen and fecal peritonitis, one had vaginal bleeding, and one had a progressive change in bowel habits. Nine patients had a long history of endometriosis, 11 patients had had hysterectomies, and eight of these had also received unopposed estrogen therapy. The lesions involved the rectum (6), sigmoid (6), colon, unspecified (2), and small intestine (3), and comprised 8 endometrioid adenocarcinomas (EA), 4 mullerian adenosarcomas (MAS), 1 endometrioid stromal sarcoma (ESS), 1 endometrioid adenofibroma of borderline malignancy (EBA) with carcinoma in situ, 2 atypical hyperplasias (AH), and one endometrioid adenocarcinoma in situ (ACIS). The tumors ranged in size from 2 to 15 cm and all involved the serosa and muscularis propria. Two tumors extended into the mucosa, with mucosal ulceration in one.
Follow-up was available in 11 cases. One patient with EA was dead of disease at 1 year, one had two recurrences at 1 and 2 years, and three were alive with no evidence of disease (ANED) at 9 months to 13 years (mean, 68 mos). The patient with the EBA was ANED at 3 months. Two patients with MAS were ANED at 2 and 3 years. The patient with ESS had a recurrence at 3 years and was ANED 6 years after her original diagnosis. One woman with AH was ANED at 60 months and the patient with ACIS was ANED at 16 months. One of the carcinomas was originally misdiagnosed as a primary intestinal adenocarcinoma.
The pathologist should be aware of the possibility of a tumor of genital tract type when evaluating intestinal neoplasms in females, particularly if they have a history of endometriosis and have received unopposed estrogen therapy.
Atypical epithelial changes and mutant p53 gene expression in ovarian endometriosis.
Bayramoglu H, Duzcan E.
Pamukkale University Faculty of Medicine, Department of Pathology, Denizli, Turkey.
Pathol Oncol Res 2001;7(1):33-8 Abstract quote
It has been reported that cases of ovarian endometriosis those with epithelial cytological atypia have potential for malignant transformation.
This study was planned to determine the incidence of atypical endometriosis and its cytological criteria, to evaluate the malignant potential of atypical endometriosis via immunohistochemical methods (p53).
In this study we evaluated 140 samples obtained from 120 cases of ovarian endometriosis and 10 ovarian endometrioid carcinomas that have been previously diagnosed histopathologically. We re-evaluated endometriosis cases with respect to their epithelial and stromal features, existence of acute or chronic inflammatory cells in endometriotic epithelium or stroma and other accompanying histological findings. We observed atypia in 7 (5.8%) cases; reactive atypia in 37 (30.8%) cases, no atypia in 76 (63.4%) cases. We evaluated immunohistochemical p53 expression in 7 atypical cases, 37 reactive atypical cases, and in 10 of those without atypia and in 10 endometrioid carcinoma cases. We noted no staining in cases with atypia, reactive atypia and without atypia while 3 cases of endometrioid carcinoma had positive staining for p53. We concluded that prominent nucleolus and angulation of nuclear contour could be added to criteria of atypia that were mentioned before in the literature.
In our study, even though p53 expression could not be shown with immunohistochemical methods in atypical endometriotic cases; it can not be determined that atypical endometriosis lesions are not premalignant. Still, endometriosis cases should be evaluated carefully by the pathologist for foci of cytological atypia and it should be kept in mind that malignant transformation might occur in these atypical endometriosis cases.
Polypoid Endometriosis: A Clinicopathologic Analysis of 24 Cases and a Review of the Literature
Parker, Robin L MD*; Dadmanesh, Farnaz MD†; Young, Robert H MD‡; Clement, Philip B MD§
From the *Department of Pathology and Laboratory Medicine, University of Calgary, and Calgary Laboratory Services, Calgary, Alberta, Canada; †Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA; ‡James Homer Wright Pathology Laboratories of the Massachusetts General Hospital, and the Department of Pathology, Harvard Medical School, Boston, MA; and §Departments of Pathology, Vancouver Hospital and Health Sciences Centre, and the University of British Columbia, Vancouver, British Columbia, Canada.
The American Journal of Surgical Pathology : Volume 28(3) March 2004 pp 285-297 Abstract quote
We describe 24 cases of polypoid endometriosis, most of which were referred because of problems in differential diagnosis, particularly distinction from a low-grade müllerian neoplasm. The patients were 23 to 78 years (mean 52.5 years) of age. Seven patients were on unopposed estrogen, four on combined estrogen-progestin therapy, and one patient had a synchronous ovarian thecoma.
The most common clinical presentations were a pelvic mass, vaginal polypoid masses, and large bowel obstruction. In some cases, the intraoperative findings suggested a neoplasm. Sites of involvement in order of frequency included colon, ovary, uterine serosa, cervical and/or vaginal mucosa, ureter, fallopian tube, omentum, bladder, paraurethral and paravaginal soft tissue, and retroperitoneum. Multiple sites were involved in seven cases.
Five cases occurred within ovarian or extraovarian endometriotic cysts. The lesions ranged up to 14 cm in size and formed polypoid, pink, gray or tan, masses. On microscopic examination, the polypoid masses were composed of an admixture of endometriotic glands and stroma. A variety of glandular architectural patterns were observed, sometimes in combination, most commonly cystic and noncystic simple hyperplasia, but also simple or complex hyperplasia with atypia, disordered proliferative, and cystic atrophy. Various types of epithelial metaplasia (tubal, mucinous, squamous, papillary syncytial metaplasia) were common.
Hemorrhage, fibrosis, prominent thick-walled blood vessels, hemosiderin-laden histiocytes, and decidual change were also present in some cases. Eighteen cases were associated with usual (nonpolypoid) endometriosis. In one case, polypoid endometriosis merged with a mucinous borderline tumor of endocervical-type. In all but two cases, polypoid endometriosis lacked periglandular stromal hypercellularity, stromal atypia, and intraglandular stromal papillae, helping distinguish it from adenosarcoma. Focal intraglandular stromal papillae were noted in two cases with focal mild periglandular stromal hypercellularity in one of them, but no stromal atypia was present in either case. Follow-up data in 17 patients indicated that 15 patients were alive without evidence of residual disease, 1 was alive with residual endometriosis, and 1 died of other causes.
In conclusion, polypoid endometriosis is a rare manifestation of endometriosis that may be mistaken for a neoplasm on clinical, intraoperative, or pathologic assessment. Some cases may be attributable to exogenous hormones or hyperestrinism and, like conventional endometriosis, some may evolve into a premalignant or, rarely, a neoplastic lesion. The main lesion in the differential is a müllerian (mesodermal) adenosarcoma.
CHARACTERIZATION Estrogen and progesterone receptors Present in glands and stroma but usually in lower concentrations than in eutopic endometrium CD10
CD10 is helpful in detecting occult or inconspicuous endometrial stromal cells in cases of presumptive endometriosis.
Groisman GM, Meir A.
Department of Pathology, Hillel Yaffe Medical Center, Hadera, Israel.
Arch Pathol Lab Med. 2003 Aug;127(8):1003-6. Abstract quote
BACKGROUND: Previous studies have shown that CD10 is a marker for normal, ectopic, and neoplastic endometrial stromal cells. However, its value in confirming a diagnosis of presumptive endometriosis has not been extensively studied.
OBJECTIVE: To assess the reactivity of CD10 in a series of cases of presumptive endometriosis and to establish the potential usefulness of this antibody in confirming the diagnosis.
DESIGN: We studied hematoxylin-eosin sections and immunoreactivity of CD10 in 20 cases diagnosed as "suspicious for," "suggestive of," or "compatible with" endometriosis as well as in 12 cases of lesions that may be confused with endometriosis (3 endosalpingioses, 3 mesothelial hyperplasias, 3 ovarian follicular cysts, and 3 hemorrhagic corpora lutea).
RESULTS: Routine sections from cases of presumptive endometriosis showed glands lacking a distinct cuff of endometrial stromal cells because of atrophy or because of changes secondary to hemorrhage, inflammation, fibrosis, and/or cystic dilatation. In a few cases, the distinction between endometrial and ovarian stroma could not be assessed with certainty. CD10 immunostaining confirmed the diagnosis in 17 (85%) of the cases, as it strongly stained endometrial stromal cells that were not apparent on hematoxylin-eosin sections. All sections from lesions that may simulate endometriosis were CD10-.
CONCLUSION: CD10 is helpful in detecting occult or inconspicuous ectopic endometrial stromal cells and in distinguishing endometriosis from its potential mimickers. We recommend its use to confirm or exclude the presence of endometrial stromal cells in cases of presumptive endometriosis and in lesions that may be mistaken for this entity.
CD44s expression is reduced in endometriotic lesions compared to eutopic endometrium in women with endometriosis.
Nothnick WB, Fan F, Iczkowski KA, Ashwell R, Thomas P, Tawfik OW.
Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160, USA.
Int J Gynecol Pathol 2001 Apr;20(2):140-6 Abstract quote
Immunohistochemical expression of the standard form of CD44 (CD44s) was examined in archival formalin-fixed endometriotic and matching eutopic endometrial tissue obtained from 25 patients in proliferative (N = 16) and secretory (N = 9) stages of the cycle. CD44s was expressed in most eutopic endometria and endometriotic tissue.
Its expression was significantly higher in secretory than in proliferative phase endometrium. It was low but detectable in 13 of 16 proliferative phase biopsies. The majority of these endometria exhibited both glandular and stromal staining (63%). In the secretory phase, glandular cells exhibited a significantly greater intensity of staining compared to stromal cells. In endometriotic tissue, stromal cell CD44s expression did not differ between tissue types in either stage of the cycle. In contrast, glandular expression in endometriotic tissue during the secretory phase was reduced (p < 0.05) compared to eutopic endometrium. It was absent in 66% of cases and reduced in the remaining cases. Our results indicate a correlation between CD44s expression and secretory differentiation of endometrial glands in the cycle, suggesting hormonal regulation of its expression.
This cyclic pattern of CD44s expression was lost in corresponding endometriotic tissue. Reduced expression of CD44s in endometriotic tissue may provide insight into the pathophysiology of endometriosis.
Utility of trichrome and reticulin stains in the diagnosis of superficial endometriosis of the uterine cervix.
Department of Diagnostic Pathology, University of Ulsan College of Medicine, Asan Medical Center, 388-1 Pungnap-dong, Songpa-gu, Seoul, 138-736, Korea.
Int J Gynecol Pathol 2001 Apr;20(2):173-6 Abstract quote
Superficial endometriosis of the uterine cervix is a not uncommon lesion and the cells on the cervicovaginal smear shed from it can be easily mistaken for cervical glandular intraepithelial neoplasia (CGIN). The correct diagnosis can not always be easily made on H&E stained tissue sections unless it is suspected. The endometriotic stroma is often misinterpreted as stromal hypercellularity or postinflammatory fibrosis following erosion or ulceration of the cervical mucosa. Moreover, the endometriotic glands may resemble tubo-endometrioid metaplasia of the endocervical glands.
This article describes the utility of trichrome and reticulin stains in the diagnosis of superficial cervical endometriosis. The absence of abundant thick collagen bundles and the investment of individual stromal cells by a fine reticulin network within the endometriotic foci are characteristic histologic features. These findings are not observed in the surrounding normal cervical stroma nor in the usual conditions in the differential diagnosis.
DIFFERENTIAL DIAGNOSIS CHARACTERIZATION CEROID GRANULOMA Ceroid Granuloma of the Uterine Cervix
Eli Pikarsky, M.D., PhD.; Bella Maly, M.D.; Alexander Maly, M.D.
From the Departments of Pathology (E.P., A.M.) and Cytology (B.M.), Jerusalem Hadassah University Hospital, Israel.
Int J Gynecol Pathol 2002;21:191-193 Abstract quote
A case of ceroid granuloma of the uterine cervix in a 58-year-old woman is presented, the fourth such case in the literature. It was an incidental finding during a routine pelvic examination and appeared as an exophytic brownish lesion on the anterior wall of the uterine cervix.
On histological examination it consisted of sheets of ceroid-rich histiocytes within the superficial cervical stroma. There was no obvious cause for the lesion.
Ceroid granulomas of the female genital tract may be related to endometriosis, but the rarity of the cases precludes definite conclusions about the etiology and pathogenesis of this lesion.
Endocervicosis of the small intestine.
Department of Pathology, Saint Agnes Medical Center, Fresno, California.
Int J Surg Pathol 2002 Jan;10(1):65-7 Abstract quote
A case of endocervicosis of the small intestine incidentally found as a mass lesion during a gastric bypass surgery is reported. No previous cases of intestinal endocervicosis have been reported in the literature.
PROGNOSIS AND TREATMENT CHARACTERIZATION PROGNOSIS Chief complications associated with pregnancy and infertility due to tubal-ovarian adhesions Ascites Serosanguineous ascites may occur with pleural effusions Spontaneous rupture May occur with cysts Malignancy
0.3-0.8% of cases of ovarian endometriosis
Endometrioid carcinoma is the most common malignancy arising in 70% of cases
Clear cell carcinoma is next most common arising in 14%
Neoplastic and pre-neoplastic changes in gastrointestinal endometriosis: a study of 17 cases.
Yantiss RK, Clement PB, Young RH.
Department of Pathology, Harvard Medical School, and the James Homer Wright Pathology Laboratories of the Massachusetts General Hospital, Boston, USA.
Am J Surg Pathol 2000 Apr;24(4):513-24 Abstract quote
The clinicopathologic features of neoplasms arising in gastrointestinal endometriosis have not been well characterized.
In this series, we report 17 cases of gastrointestinal endometriosis complicated by neoplasms (14 cases) or precancerous changes (three cases). Four patients, one of whom also had hypermenorrhea, presented with chronic abdominal pain and five had obstructive symptoms; one of these also had rectal bleeding. One patient presented with an acute abdomen and fecal peritonitis, one had vaginal bleeding, and one had a progressive change in bowel habits. Nine patients had a long history of endometriosis, 11 patients had had hysterectomies, and eight of these had also received unopposed estrogen therapy.
The lesions involved the rectum (6), sigmoid (6), colon, unspecified (2), and small intestine (3), and comprised 8 endometrioid adenocarcinomas (EA), 4 mullerian adenosarcomas (MAS), 1 endometrioid stromal sarcoma (ESS), 1 endometrioid adenofibroma of borderline malignancy (EBA) with carcinoma in situ, 2 atypical hyperplasias (AH), and one endometrioid adenocarcinoma in situ (ACIS). The tumors ranged in size from 2 to 15 cm and all involved the serosa and muscularis propria. Two tumors extended into the mucosa, with mucosal ulceration in one. Follow-up was available in 11 cases. One patient with EA was dead of disease at 1 year, one had two recurrences at 1 and 2 years, and three were alive with no evidence of disease (ANED) at 9 months to 13 years (mean, 68 mos). The patient with the EBA was ANED at 3 months. Two patients with MAS were ANED at 2 and 3 years. The patient with ESS had a recurrence at 3 years and was ANED 6 years after her original diagnosis. One woman with AH was ANED at 60 months and the patient with ACIS was ANED at 16 months. One of the carcinomas was originally misdiagnosed as a primary intestinal adenocarcinoma.
The pathologist should be aware of the possibility of a tumor of genital tract type when evaluating intestinal neoplasms in females, particularly if they have a history of endometriosis and have received unopposed estrogen therapy.
Endometriosis-associated intestinal tumors: a clinical and pathological study of 6 cases with a review of the literature.
Slavin RE, Krum R, Van Dinh T.
Cascade Pathology Group, Legacy Portland Hospitals, OR, USA.
Hum Pathol 2000 Apr;31(4):456-63 Abstract quote
This clinicopathologic study of primary Mullerian tumors of the bowel arising in foci of endometriosis is based on six new cases and an analysis of 17 previously reported cases.
Varieties of Mullerian tumors occur in the bowel; the most common types are endometrioid carcinoma, followed by various mixed Mullerian tumors and stromal sarcomas. Seventy-eight percent develop in the rectosigmoid colon, the remaining in the cecum or ileum. Those in the latter area tend to be sarcomas or mixed Mullerian tumors. Certain architectural growth characteristics, derived from precursor endometriosis, are common to most endometriosis-associated intestinal tumors (EAITs). Seventy percent of EAITs occur in the outer bowel wall. Transmural tumors tend to form luminal polyps and assume an hourglass shape.
Metachronous or synchronous Mullerian tumors occur in 39% of cases. Seventy percent of women with EAITs are in their mid 30s to early 50s. Common presenting symptoms are abdominal or pelvic pain, melena, and an abdominal or pelvic mass. Documented in 26% of patients is a history of prolonged unopposed estrogen therapy. Only 28.5% of cases die of their tumors, but follow-up is less than 5 years in all but 2 patients.
Malignancy in endometriosis: frequency and comparison of ovarian and extraovarian types.
Stern RC, Dash R, Bentley RC, Snyder MJ, Haney AF, Robboy SJ.
Department of Pathology, Duke University Medical Center, Box 3712, Durham, NC 27710, USA.
Int J Gynecol Pathol 2001 Apr;20(2):133-9 Abstract quote
One thousand consecutive cases of surgically proven endometriosis were reviewed to evaluate the frequency and types of pelvic cancers that were associated with ovarian and extraovarian endometriosis. The frequency and types of histologic abnormalities present in the eutopic endometrium when cancers were noted in endometriosis were also evaluated.
In the large subset of cases for which the authors were the primary pathologists and all foci of endometriosis were recorded, the frequency of malignancy was 10.8%. In contrast, the frequency was only 3.2% in cases diagnosed by others previously in our institution. Cancers were more commonly found in ovaries when endometriosis was present in that ovary (5%) compared to when endometriosis was present at other sites (1%).
Clear cell and endometrioid carcinomas were the malignancies most commonly seen in ovaries containing endometriosis, while clear cell adenocarcinoma and adenosarcoma were most commonly seen in conjunction with extraovarian endometriosis. The association of endometriosis with endometrioid and clear cell carcinoma was much stronger than that of serous and mucinous tumors (p < .01). Concurrent endometrial pathology was commonly seen in cases of malignant transformation of endometriosis (32% of cases).
The gonadotropin-releasing hormone agonist leuprolide acetate induces apoptosis and suppresses cell proliferative activity in rectovaginal endometriosis.
Mizutani T, Sugihara A, Nakamuro K, Suehara N, Terada N.
Department of Obstetrics, Osaka Medical Center, Japan.
Am J Obstet Gynecol 1999 Sep;181(3):750-1 Abstract quote
A gonadotropin-releasing hormone agonist, leuprolide acetate, was administered every 4 weeks for treatment of rectovaginal endometriosis. Degrees of apoptosis (percentage of in situ deoxyribonucleic acid 3'-end-labeled cells) and cell proliferative activity (percentage of cells with immunostaining for proliferating cell protein Ki-67) were examined in endometriotic glands of biopsy specimens taken before and during gonadotropin-releasing hormone agonist therapy.
Gonadotropin-releasing hormone agonist induced apoptosis and suppressed cell proliferative activity in endometriotic glands.
Laparoscopic treatment of complete obliteration of the cul-de-sac associated with endometriosis: long-term follow-up of en bloc resection.
Redwine DB, Wright JT.
Endometriosis Treatment Program, St. Charles Medical Center, Bend, Oregon, USA.
Fertil Steril 2001 Aug;76(2):358-65 Abstract quote
OBJECTIVE: To evaluate symptom relief following a laparoscopic technique designed for treatment of complete obliteration of the cul-de-sac associated with endometriosis, with fertility preserved.
DESIGN: Preoperative and postoperative questionnaire study of a cohort of patients with complete obliteration of the cul-de-sac undergoing a standardized laparoscopic surgical treatment.
SETTING: American tertiary referral center for the surgical treatment of endometriosis.
PATIENTS: Eighty-four consecutive patients undergoing laparoscopic treatment of endometriosis with complete cul-de-sac obliteration with 67 replying to a postoperative questionnaire.
INTERVENTIONS: Laparoscopic excision of all endometriosis including treatment of complete obliteration of the cul-de-sac by en bloc resection and bowel resection as needed.
MAIN OUTCOME MEASURES: Symptom relief as measured on a 5-point ranked ordinal scale administered before and after surgery, as well as perioperative complications, postoperative fertility, and prognostic value of preoperative findings on pelvic examination.
RESULTS: Symptom reduction was obtained for all symptoms related to cul-de-sac disease, particularly for patients with severe or debilitating symptoms preoperatively. There was no significant complication, and the postoperative fertility rate was 43%. Seventy-three percent of patients with obliteration of the cul-de-sac had histologically proved rectal endometriosis. Nodularity and tenderness on examination were predictive of symptom improvement.
CONCLUSIONS: Aggressive laparoscopic excision of endometriosis carried out in a specialist center offers good symptom relief, especially for those with severe or debilitating symptoms. To ensure complete removal of all disease, intestinal surgery is required in most patients with complete obliteration of the cul-de-sac.
Treating endometriosis as an autoimmune disease.
Department of Obstetrics and Gynecology, University of Kansas Medical Center, Kansas City, Kansas 66160, USA.
Fertil Steril 2001 Aug;76(2):223-31 Abstract quote
OBJECTIVE: To review the literature on the role of autoimmunity in the etiology of endometriosis, compare the similarities in the pathophysiologies between endometriosis and autoimmune diseases, and discuss the use of immunomodulators currently used to treat autoimmune diseases as potential therapies for endometriosis.
DESIGN: The literature on endometriosis and other autoimmune diseases was reviewed, and summary data are presented.
RESULTS: Endometriosis shares many similarities with autoimmune diseases such as rheumatoid arthritis, Crohn's disease, and psoriasis. These similarities include elevated levels of cytokines, decreased cell apoptosis, and T- and B-cell abnormalities. Because the use of immunomodulators and inflammatory modulators has proven to be an effective means of medical management for these autoimmune diseases, similar therapies may prove useful in treating endometriosis.
CONCLUSION(S): Although substantial evidence indicates that endometriosis at least shares many similarities with autoimmune diseases, endometriosis is primarily treated by using compounds that induce a hypoestrogenic environment. A review of the literature combined with the shortcomings of current means of medical management for endometriosis support the postulate that treatment of endometriosis with immunomodulators and inflammatory modulators is warranted.
Persisting active and proliferative intrinsic ureteral endometriosis under GNRH agonists therapy: a case with immunohistological study.
Anaf V, Vanden Bossche MV, Simon P, Riera C, Fayt I, Noel JC.
Department of Gynaecology, Hospital Erasme, Universite Libre de Bruxelles (ULB), 808 route de Lennik, 1070, Brussels, Belgium.
Eur J Obstet Gynecol Reprod Biol 2001 Aug;97(2):250-4 Abstract quote
We report the case of a 30-year-old patient who underwent a segmental ureteral resection with ureteroureterostomy because of the presence of a left ureterohydronephrosis caused by an intrinsic ureteral endometriotic lesion.
Preoperatively, the patient received a 3 months course of GNRH agonists. The serum estradiol level was at 12 pg/ml at the moment of surgery. Histology and immunohistochemistry performed on the resected specimen showed the presence of numerous large haemorrhagic endometriotic foci containing very high levels of alpha-estrogen and progesterone nuclear receptors, a high Ki-67 labeling index and a strong positivity for EGF-receptor. This is the first report of immunohistochemical study performed on ureteral endometriosis preoperatively treated with GNRH agonists.
Because hormonal treatments are often prescribed in the treatment of ureteral endometriosis, clinicians should be aware of the possibility of persisting very active and proliferative ureteral endometriotic lesions even under treatment with GNRH agonists and very low levels of circulating estradiol.
Macpherson and Pincus. Clinical Diagnosis and Management by Laboratory Methods. Twentyfirst Edition. WB Saunders. 2006.
Rosai J. Ackerman's Surgical Pathology. Ninth Edition. Mosby 2004.
Sternberg S. Diagnostic Surgical Pathology. Fourth Edition. Lipincott Williams and Wilkins 2004.
Robbins Pathologic Basis of Disease. Seventh Edition. WB Saunders 2005.
DeMay RM. The Art and Science of Cytopathology. Volume 1 and 2. ASCP Press. 1996.
Weedon D. Weedon's Skin Pathology Second Edition. Churchill Livingstone. 2002
Fitzpatrick's Dermatology in General Medicine. 6th Edition. McGraw-Hill. 2003.
Weiss SW and Goldblum JR. Enzinger and Weiss's Soft Tissue Tumors. Fourth Edition. Mosby 2001.
Adhesions-These are the fibrous bands of scar tissue that form on the surfaces of organs and between organs. They result from inflammation, scarring, and subsequent healing. Adhesions may cause pain and life threatening conditions if vital organs are trapped or encased within them.
Chocolate Cyst-This is endometriosis involving an ovary leading to hemorrhage and blood clot. As the blood clot ages, it breaks down to form a dark red to black appearance.
Hemosiderin-This is a breakdown product of hemoglobin, the oxygen carrying molecule within red blood cells. If the hemosiderin is engulfed by macrophages, the scavenger cells of the immune system, the term hemosiderin laden macrophages is used.
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