ABSTRACT
Mesonephric adenocarcinomas (MAs) and mesonephric-like adenocarcinomas (MLAs) are rare, aggressive neoplasms that arise in the gynecologic tract and show overlapping morphologic, immunohistochemical, and molecular features. While MAs occur in the cervix and are thought to arise from mesonephric remnants, MLAs occur in the endometrium and ovary and are believed to originate from transdifferentiation of Müllerian lesions. Both MAs and MLAs show a variety of architectural patterns, exhibit frequent expression of GATA3 by immunohistochemistry, and harbor KRAS mutations. In a recent article published in The Journal of Pathology, Kommoss and colleagues used DNA methylation profiling to extend these similarities and showed that MLAs and MAs cluster together based on their epigenetic signatures and are epigenetically distinct from other Müllerian adenocarcinomas. They also showed that MLAs and MAs harbor a high number of global copy number alterations. This study provides evidence that MLAs more closely resemble MAs than Müllerian carcinomas on an epigenetic level. As a result, the authors argue that MLA should be renamed 'mesonephric-type adenocarcinoma.' Further research is needed to establish the relationship between these two entities, their etiology, and pathogenesis. © 2024 The Pathological Society of Great Britain and Ireland.
Subject(s)
Adenocarcinoma , DNA Methylation , Epigenesis, Genetic , Uterine Cervical Neoplasms , Humans , Adenocarcinoma/genetics , Adenocarcinoma/pathology , Female , Uterine Cervical Neoplasms/genetics , Uterine Cervical Neoplasms/pathology , Mullerian Ducts/pathology , Mesonephroma/genetics , Mesonephroma/pathology , Biomarkers, Tumor/genetics , EpigenomeABSTRACT
Anatomically, normal cells found in an abnormal site are known as choristoma. When any two of the three-cell lineage of the mullerian duct, that is endosalpinx, endocervix and endometrium, are found at an abnormal location, it is termed mullerian choristoma or mullerianosis. Mullerianosis histologically reveals glands of varying sizes lined by cervical, tubal and endometrial cells. Individual cell lineages like endometriosis of the ovary, endosalpingiosis and endocervicosis of the urinary bladder are common. But mullerianosis is quite rare, and as per literature, only about 20 cases have been reported. We report a mullerianosis involving the liver and lung in a 41-year-old female that mimicked metastatic biliary cystadenocarcinoma. It is the first case reported in literature where there is simultaneous involvement of the liver and lung by mullerianosis. The diagnosis was made with the help of histopathology and immunohistochemistry in the resected specimens.
Subject(s)
Choristoma , Cystadenocarcinoma , Lung Neoplasms , Mullerian Ducts , Humans , Female , Adult , Diagnosis, Differential , Mullerian Ducts/pathology , Choristoma/diagnosis , Choristoma/pathology , Cystadenocarcinoma/diagnosis , Cystadenocarcinoma/pathology , Lung Neoplasms/diagnosis , Lung Neoplasms/pathology , Lung Neoplasms/secondary , Liver Neoplasms/diagnosis , Liver Neoplasms/secondary , Liver Neoplasms/pathologyABSTRACT
Mullerianosis is a rare, complex, benign tumor most commonly found in the bladder and often mistaken for a neoplastic lesion. Herein, we report a case of mullerianosis in a 65-year-old woman who presented with an incidental 2 cm bladder mass found on cross-sectional imaging. A mixed cystic and solid tumor was identified on cystoscopy and a transurethral resection of the suspected tumor was performed with histopathology confirming a final diagnosis of mullerianosis. While an unusual diagnosis, mullerianosis of the urinary bladder needs to be correctly identified to provide appropriate treatment and avoid misdiagnosis.
Subject(s)
Neoplasms , Urinary Bladder Diseases , Female , Humans , Aged , Urinary Bladder/diagnostic imaging , Urinary Bladder/surgery , Mullerian Ducts/pathology , Urinary Bladder Diseases/diagnosis , Urinary Bladder Diseases/surgery , Urinary Bladder Diseases/pathology , CystoscopyABSTRACT
Serous cystadenoma is a rare lesion in the para-testicular tissue, with even rarer reports of this entity occurring in the scrotum post-orchidopexy. We present such an occurrence, adding support for its existence as a distinct entity.
Subject(s)
Cystadenoma, Serous , Genital Neoplasms, Male , Orchiopexy , Scrotum , Humans , Male , Scrotum/pathology , Cystadenoma, Serous/pathology , Cystadenoma, Serous/diagnosis , Cystadenoma, Serous/surgery , Genital Neoplasms, Male/pathology , Genital Neoplasms, Male/diagnosis , Genital Neoplasms, Male/surgery , Mullerian Ducts/pathology , Mullerian Ducts/abnormalitiesABSTRACT
Persistent Müllerian Duct syndrome is a rare male disorder of sexual development. The phenotypically and genotypically male patient presents with female internal organs (i.e., uterus, cervix, fallopian tubes and upper part of vagina) due to deficiency of anti-mullerian hormone or insensitivity of tissues to Anti Mullerian Hormone. We present a 19 year old male who came with complaint of right iliac fossa pain. He was investigated for acute appendicitis and on imaging, he was diagnosed to have bilateral cryptorchidism with rudimentary uterus. Computed tomography followed by pelvic ultrasonography was done which indicated two testes in abdomen and a soft tissue density structure, identified as a rudimentary uterus located posterior to the urinary bladder. CT scan findings were further confirmed by magnetic resonance imaging pelvis. A trial of stepwise orchidopexy followed by orchidectomy with removal of rudimentary uterus was performed laparoscopically. Additionally, he was counselled for long term sex hormone replacement and reproductive failure in future.
Subject(s)
Cryptorchidism , Disorder of Sex Development, 46,XY , Humans , Male , Female , Young Adult , Adult , Disorder of Sex Development, 46,XY/diagnosis , Disorder of Sex Development, 46,XY/surgery , Cryptorchidism/diagnosis , Cryptorchidism/surgery , Anti-Mullerian Hormone , Mullerian Ducts/surgery , Mullerian Ducts/pathologyABSTRACT
Cysts in the lesser pelvis are a rare disease and most often an incidental finding from routine diagnostic investigation. Published information is controversial. These cysts are distinguished by localisation, content of the cyst and accompanying anatomical anomalies. In this case, we report a 33 years old man who presented to our clinic due to a large retrovesical cyst. Because of lower abdominal pain and problems with defecation, the cyst was diagnosed by ultrasound. Further radiological diagnostic testing confirmed the presence of a retrovesical cyst of unknown malignancy, which was retrospectively evaluated as a Müllerian duct cyst. Due to symptoms and potential malignancy of the cyst, the decision was made to perform surgery. With the help of the operation robot, this benign cyst was safely and completely removed. In a follow-up, the patient presented free of symptoms and sonographically there was no sign of recurrence. Therefore robotic-assisted resection is a safe procedure to treat large symptomatic Müllerian duct cysts.
Subject(s)
Cysts , Robotic Surgical Procedures , Male , Humans , Adult , Mullerian Ducts/surgery , Mullerian Ducts/pathology , Retrospective Studies , Cysts/surgery , Cysts/diagnosis , Cysts/pathology , UltrasonographyABSTRACT
Mullerian cysts are benign tumors that are very rare in the posterior mediastinum. It is necessary to distinguish Mullerian cysts from benign tumors or other types of cyst in the posterior mediastinum. A 42-year-old woman visited our hospital for a routine check-up, and a mediastinal mass was identified on chest computed tomography (CT). Contrast-enhanced chest magnetic resonance imaging (MRI) revealed a 4.0 × 2.6 × 2.8-cm mass, and a neurogenic tumor or esophageal cyst was suspected. Single-port thoracoscopic surgery was performed for cyst removal. Histopathological examination of the resected tissue revealed that the cyst wall was covered with a single layer of ciliated columnar epithelium. Immunohistochemical staining revealed positivity for paired box gene 8 (PAX8), Wilms tumor protein 1 (WT-1), estrogen receptor (ER), and progesterone receptor (PR). Therefore, a diagnosis of mediastinal Mullerian cyst was made. Mediastinal Mullerian cysts should be included in the differential diagnosis of posterior mediastinal cysts. Cystic lesions in the posterior mediastinum should be removed surgically and undergo immunohistochemical examination.
Subject(s)
Mediastinal Cyst , Adult , Female , Humans , Magnetic Resonance Imaging , Mediastinal Cyst/diagnostic imaging , Mediastinal Cyst/surgery , Mediastinum/pathology , Mullerian Ducts/metabolism , Mullerian Ducts/pathology , Mullerian Ducts/surgery , Tomography, X-Ray ComputedABSTRACT
Mullerian cysts are mostly described in women, near the genitourinary organs. Exceptional cases of retroperitoneal and posterior mediastinal located Mullerian cysts have been reported. When located in the retroperitoneum, those cysts are often confused with other retroperitoneal cysts such as cystic lymphangioma and cystic mesothelioma of peritoneum because of the poor clinical picture and a nonspecific radiologic presentation. The histopathological analysis is essential to make the diagnosis, and the positive staining of a Müllerian marker is a decisive argument in favor of a Müllerian cyst. Here, we report a case of an incidental finding of a retroperitoneal Müllerian cyst in a 68-years-old woman.
Subject(s)
Cysts , Incidental Findings , Humans , Female , Aged , Mullerian Ducts/pathology , Retroperitoneal Space/pathology , Cysts/diagnosis , Cysts/pathologyABSTRACT
Müllerian anomaly (M.A.) is a group of congenital anatomic abnormalities caused by aberrations of the development process of the Müllerian duct. M.A. can either be isolated or be involved in Mendelian syndromes, such as Dandy-Walker syndrome, Holt-Oram syndrome and Bardet-Biedl syndrome, which are often associated with both uterus and kidney malformations. In this study, we applied a genotype-first approach to analyze the whole-exome sequencing data of 492 patients with M.A. Six potential pathogenic variants were found in five genes previously related to female urogenital deformities (PKD1, SON, SALL1, BMPR1B, ITGA8), which are partially overlapping with our patients' phenotypes. We further identified eight incidental findings in seven genes related to Mendelian syndromes without known association with reproductive anomalies (TEK, COL11A1, ANKRD11, LEMD3, DLG5, SPTB, BMP2), which represent potential phenotype expansions of these genes.
Subject(s)
Abnormalities, Multiple , Lower Extremity Deformities, Congenital , Upper Extremity Deformities, Congenital , Abnormalities, Multiple/genetics , Abnormalities, Multiple/pathology , Female , Genotype , Humans , Lower Extremity Deformities, Congenital/genetics , Mullerian Ducts/abnormalities , Mullerian Ducts/pathology , Upper Extremity Deformities, Congenital/geneticsABSTRACT
BACKGROUND: Congenital multisystemic lesions with co-occurrence of non-random malformations, such as VACTERL-H or MURCS association, often pose serious threads to the newborn and still constitute an antenatal diagnostic dilemma. CASE REPORT: A malformed fetus with VACTERL-H association at 20 gestational weeks had a skin-covered neural tube defect (NTD) of the lower cervical spine, concomitant hydrocephalus, as well as unilateral multicystic dysplastic kidney and the suspicion of mullerian duct anomaly as potentially assigned to MURCS association. DISCUSSION/CONCLUSION: We were able to demonstrate how well-defined, standardized volumetric reconstruction of diagnostic views displaying fetal pathology in utero might aid early and precise diagnosis of multi-organ malformations. Application of modern diagnostic imaging tools is helpful in delineation of the most likely diagnoses (VACTERL-H vs. MURCS) as further specified during detailed pathologic work-up and might consequently facilitate individually tailored interdisciplinary counseling, as in the case presented here.
Subject(s)
Abnormalities, Multiple , Heart Defects, Congenital , Hydrocephalus , Limb Deformities, Congenital , Multicystic Dysplastic Kidney , 46, XX Disorders of Sex Development , Abnormalities, Multiple/diagnosis , Abnormalities, Multiple/pathology , Anal Canal/abnormalities , Cardiovascular Abnormalities , Congenital Abnormalities , Digestive System Abnormalities , Esophagus/abnormalities , Female , Fetus/pathology , Genetic Diseases, X-Linked , Heart Defects, Congenital/pathology , Humans , Hydrocephalus/diagnosis , Hydrocephalus/pathology , Kidney/abnormalities , Kidney/pathology , Limb Deformities, Congenital/diagnosis , Mullerian Ducts/abnormalities , Mullerian Ducts/pathology , Multicystic Dysplastic Kidney/complications , Multicystic Dysplastic Kidney/diagnosis , Multicystic Dysplastic Kidney/pathology , Musculoskeletal Abnormalities , Pregnancy , Spine/abnormalities , Spine/pathology , Trachea/abnormalitiesABSTRACT
Mesonephric-like adenocarcinomas (MLA) are rare neoplasms arising in the uterine corpus and ovary which have been added to the recent 2020 World Health Organization Classification of Female Genital Tumors. They have similar morphology and immunophenotype and exhibit molecular aberrations similar to cervical mesonephric adenocarcinomas. It is debated as to whether they are of mesonephric or Mullerian origin. We describe the clinical, pathologic, immunohistochemical, and molecular features of 5 cases of extrauterine mesonephric-like proliferations (4 ovary, 1 extraovarian), all with novel and hitherto unreported features. These include an origin of MLA in extraovarian endometriosis, an association of ovarian MLA with high-grade serous carcinoma, mixed germ cell tumor and mature teratoma, and a borderline ovarian endometrioid tumor exhibiting mesonephric differentiation. Four of the cases exhibited a KRAS variant and 3 also a PIK3CA variant. In reporting these cases, we expand on the published tumor types associated with MLA and report for the first time a borderline tumor exhibiting mesonephric differentiation. We show the value of molecular testing in helping to confirm a mesonephric-like lesion and in determining the relationship between the different neoplastic components. We provide further evidence for a Mullerian origin, rather than a true mesonephric origin, in some of these cases. We also speculate that in the 2 cases associated with germ cell neoplasms, the MLA arose out of the germ cell tumor.
Subject(s)
Adenocarcinoma/pathology , Mullerian Ducts/pathology , Ovarian Neoplasms/pathology , Peritoneal Neoplasms/pathology , Wolffian Ducts/pathology , Adenocarcinoma/chemistry , Adenocarcinoma/genetics , Adenocarcinoma/therapy , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/analysis , Biomarkers, Tumor/genetics , Cell Differentiation , Cell Proliferation , Class I Phosphatidylinositol 3-Kinases/genetics , Female , Humans , Mesocolon/chemistry , Mesocolon/pathology , Middle Aged , Mullerian Ducts/chemistry , Mutation , Ovarian Neoplasms/chemistry , Ovarian Neoplasms/genetics , Ovarian Neoplasms/therapy , Peritoneal Neoplasms/chemistry , Peritoneal Neoplasms/genetics , Peritoneal Neoplasms/therapy , Proto-Oncogene Proteins p21(ras)/genetics , Treatment Outcome , Wolffian Ducts/chemistryABSTRACT
Congenital anomalies of the female reproductive tract that present with primary amenorrhea involve Müllerian aplasia, also known as Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS), and cervical and vaginal anomalies that completely obstruct the reproductive tract. Karyotype abnormalities do not exclude the diagnosis of MRKHS. Familial cases of Müllerian anomalies and associated malformations of the urinary and skeletal systems strongly suggest a complex genetic etiology, but so far, the molecular mechanism in the vast majority of cases remains unknown. Primary amenorrhea may also be the first presentation of complete androgen insensitivity syndrome, steroid 5α-reductase type 2 deficiency, 17ß-hydroxysteroid dehydrogenase type 3 deficiency, and Leydig cells hypoplasia type 1; therefore, these disorders should be considered in the differential diagnosis of the congenital absence of the uterus and vagina. The molecular diagnosis in the majority of these cases can be established.
Subject(s)
46, XX Disorders of Sex Development/pathology , Amenorrhea/genetics , Amenorrhea/pathology , Cervix Uteri/abnormalities , Congenital Abnormalities/pathology , Mullerian Ducts/abnormalities , Vagina/abnormalities , 17-Hydroxysteroid Dehydrogenases/deficiency , 17-Hydroxysteroid Dehydrogenases/genetics , Androgen-Insensitivity Syndrome/genetics , Androgen-Insensitivity Syndrome/pathology , Cervix Uteri/embryology , Cholestenone 5 alpha-Reductase/deficiency , Cholestenone 5 alpha-Reductase/genetics , Congenital Abnormalities/diagnosis , Disorder of Sex Development, 46,XY/genetics , Disorder of Sex Development, 46,XY/pathology , Female , Humans , Male , Mullerian Ducts/pathology , Testis/abnormalities , Testis/pathology , Vagina/embryologyABSTRACT
A 20-year-old male presented to the emergency department with lower abdominal pain, urinary retention, and constipation. Computed tomography (CT) revealed a large cyst on the posterior aspect of the prostate gland; he was ultimately diagnosed with a Müllerian duct cyst (MDC). Although much has been written on the radiologic diagnosis of such cysts, there is a paucity of recent literature concerning the pathological diagnosis. While older studies debated the Müllerian origin of a midline cyst abutting the poster prostate, we believe that with the advent of monoclonal PAX8 (which was positive in this lesion) and monoclonal PAX2 (which was negative), we have strong evidence that the present cyst is indeed of Müllerian origin. Further, there is debate in the literature as to whether MDC is synonymous or distinct from prostatic utricle cyst. We present an interdisciplinary analysis as to the merits and weaknesses of both sides of the debate and how data gathered from the current case could be used in a future, larger study to arrive at a more definitive conclusion.
Subject(s)
Cysts/pathology , Mullerian Ducts/pathology , Prostatic Diseases/diagnosis , Prostatic Diseases/pathology , Biomarkers/metabolism , Humans , Immunohistochemistry , Male , PAX8 Transcription Factor/biosynthesis , Young AdultABSTRACT
BACKGROUND: Inguinal hernia containing ovary and fallopian tube can be found in paediatric population and is a rare finding in women of reproductive age group. Most of the cases are associated with congenital abnormalities of the female genital tract. CASE PRESENTATION: A 20 year old female presented with right reducible inguinal hernia, primary amenorrhea and normal secondary sexual characteristics. Clinical examination revealed scoliosis with convexity towards left side, prominence of left rib cage with Sprengel deformity and right sided heart sounds. Ultrasound of the inguinal swelling revealed right ovary within the hernial sac, Chest X-ray revealed right lung collapse and dextrocardia. Further Magnetic resonance imaging (MRI) of pelvis revealed inguinal hernia with right ovary as its content, normal left ovary and absent uterus. Computed tomography (CT) revealed complete collapse of right lung with compensatory left lung hyperinflation and absent right kidney. Karyotyping of the patient was normal, 46XX. A diagnosis of MURCS syndrome with right ovarian hernia was made. The hernia was surgically managed with repositioning of ovary and fallopian tube into the pelvis. DISCUSSION: Ovary in inguinal hernia is rare in women of reproductive age group. MRKH syndrome, a mullerian duct anomaly, is the congenital aplasia of uterus and upper two-thirds of vagina in a female with normal ovaries, fallopian tube, secondary sexual characteristics and 46XX karyotype. MURCS is a subtype of MRKH type 2 having mullerian duct agenesis with renal, cardiac, muscular & vertebral defects. General physical examination and primary investigations if yields abnormal findings; the patient must undergo an array of investigations to rule out MRKH/MURCS, or other congenital abnormality. Early diagnosis is essential to prevent its incarceration or torsion. The primary treatment of ovary in inguinal hernia is repositioning the ovary and fallopian tube back to pelvis to preserve fertility and repair of inguinal hernia. A multidisciplinary team is required to deal with various abnormalities present in a patient with MURCS.
Subject(s)
46, XX Disorders of Sex Development/complications , Hernia, Inguinal/etiology , Mullerian Ducts/abnormalities , Ovarian Diseases/pathology , 46, XX Disorders of Sex Development/pathology , Adult , Congenital Abnormalities/pathology , Female , Hernia, Inguinal/pathology , Humans , Mullerian Ducts/pathology , Young AdultABSTRACT
OBJECTIVES: Antimullerian hormone (AMH) causes regression of the mullerian ducts in the male fetus. The appendix testis (AT) is a vestigial remnant of mullerian duct origin, containing both androgen (AR) and estrogen (ER) receptors. The role of both AMH and AT in testicular descent is yet to be studied. We investigated the possible association of AMH with AT size, the AR and ER, and their expression in the AT, in congenital cryptorchidism. METHODS: A total of 26 patients with congenital unilateral cryptorchidism and 26 controls with orthotopic testes were investigated, and 21 ATs were identified in each group. AMH and insulin-like three hormone (INSL3) concentrations were measured with spectrophotometry. AR and ER receptor expression was assessed with immunohistochemistry using monoclonal antibodies R441 for AR and MAB463 for ER. For the estimation of receptor expression, the Allred Score method was used. RESULTS: AMH concentrations did not present significant differences between patients with congenital cryptorchidism and the controls. Also, no correlation was found between AMH, INSL3, and AT length. Allred scores did not present significant differences. However, expression percentiles and intensity for both receptors presented significant differences. Three children with cryptorchidism and the highest AMH levels also had the highest estrogen receptor scores in the AT. CONCLUSIONS: No association was found between AMH and the studied major parameters. However, higher AMH concentrations, in combination with higher estrogen receptor scores in the AT, may play a role in cryptorchidism in some children. Larger population samples are needed to verify this observation.
Subject(s)
Anti-Mullerian Hormone/blood , Cryptorchidism/pathology , Genitalia, Male/pathology , Receptors, Androgen/genetics , Receptors, Estrogen/genetics , Child, Preschool , Cohort Studies , Cryptorchidism/blood , Cryptorchidism/genetics , Gene Expression , Genitalia, Male/abnormalities , Genitalia, Male/embryology , Greece , Humans , Infant , Insulin/blood , Male , Mullerian Ducts/abnormalities , Mullerian Ducts/metabolism , Mullerian Ducts/pathology , Organ Size , Proteins , Receptors, Androgen/metabolism , Receptors, Estrogen/metabolism , Testis/abnormalities , Testis/pathologyABSTRACT
Mayer-Rokitansky-Küster-Hauser (MRKH) Syndrome is a sex development disorder that affects 1 in every 4500 46, XX live births. At least a subset of MRKH syndrome is genetically related to which various candidate genes have been identified. The growth regulation by estrogen in breast cancer 1-like gene (GREB1L) is an androgen-regulated gene reported to be a co-activator of the retinoic acid receptor gene (RAR). Thus expression levels of GREB1L have implications on renal system cellular differentiation, morphogenesis, and homeostasis in vertebrates. Variants of GREB1L have been reported in familial and sporadic MRKH Syndrome and more importantly, in a three-generation family ofMRKH syndrome propositae. Much the same way, Mutants of GREB1L have also been identified in isolated bilateral renal agenesis and deafness both of which are extra-genital tract anomalies in MRKH type 2. Again, renal agenesis transgenic mice have been produced from an E13.5 CRISPR/cas9 GREB1L mutagenesis. Though no GREB1L mutation has been reported in cardiac malformation, there is evidence that GREB1L is involved in ventricular development. Here, we intorigate evidence that projects GREB1L as a candidate gene of Mayer-Rokitansky-Küster-Hauser Syndrome and propose that functional validation analysis to that effect is imparative.
Subject(s)
46, XX Disorders of Sex Development/genetics , Congenital Abnormalities/genetics , Mullerian Ducts/abnormalities , Neoplasm Proteins/genetics , 46, XX Disorders of Sex Development/pathology , Animals , Congenital Abnormalities/pathology , Humans , Mullerian Ducts/pathology , Mutation , Neoplasm Proteins/metabolism , PhenotypeABSTRACT
PURPOSE: Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome consists of congenital absence of the uterus and vagina and is often associated with renal, skeletal, cardiac, and auditory defects. The genetic basis is largely unknown except for rare variants in several genes. Many candidate genes have been suggested by mouse models and human studies. The purpose of this study was to narrow down the number of candidate genes. METHODS: Whole exome sequencing was performed on 111 unrelated individuals with MRKH; variant analysis focused on 72 genes suggested by mouse models, human studies of physiological candidates, or located near translocation breakpoints in t(3;16). Candidate variants (CV) predicted to be deleterious were confirmed by Sanger sequencing. RESULTS: Sanger sequencing verified 54 heterozygous CV from genes identified through mouse (13 CV in 6 genes), human (22 CV in seven genes), and translocation breakpoint (19 CV in 11 genes) studies. Twelve patients had ≥ 2 CVs, including four patients with two variants in the same gene. One likely digenic combination of LAMC1 and MMP14 was identified. CONCLUSION: We narrowed 72 candidate genes to 10 genes that appear more likely implicated. These candidate genes will require further investigation to elucidate their role in the development of MRKH.
Subject(s)
46, XX Disorders of Sex Development/genetics , Congenital Abnormalities/genetics , Mullerian Ducts/abnormalities , Uterus/abnormalities , Vagina/abnormalities , 46, XX Disorders of Sex Development/pathology , Animals , Congenital Abnormalities/pathology , Female , Genetic Variation , Humans , Male , Mice , Mullerian Ducts/pathology , Translocation, Genetic , Exome SequencingABSTRACT
We describe a case of Beckwith-Wiedemann syndrome (BWS) demonstrating pre- and post-natal intra-familial variability. Our first encounter with the family occurred in the 1990s following the birth of 3 affected offspring. The first two pregnancies presented with exomphalos and elevated second trimester maternal serum alpha-fetoprotein (msAFP, 3.43 and 4.01 MOM, respectively) as well as elevated maternal human chorionic gonadotrophin (mhCG, 4.33 and 8.8 MOM, respectively). The diagnosis of BWS was confirmed postnatally in both cases. The third ongoing pregnancy presented only with elevated mhCG (7.09 MOM) and no malformation. Nonetheless BWS was suspected. The diagnosis was confirmed postnatally with clinical manifestations including macroglossia and cleft palate. Two affected female siblings were also diagnosed with Mullerian agenesis in adulthood. Suspecting a common genetic etiology, sequencing of the CDKN1C gene revealed a maternally inherited, likely pathogenic variant (NM_000076.2: c.367_385del; p.(Ala123Serfs*143)) causative of BWS. Chromosomal microarray and whole exome sequencing did not reveal any other pathogenic variant that would explain the Mullerian agenesis. One of the affected females underwent successful preimplantation genetic testing (PGT) with a surrogate and gave birth to a healthy female. To the best of our knowledge, this is the first report of Mullerian agenesis as a possible rare expansion of the BWS phenotype. In addition, this case highlights the potential role of abnormal second trimester biochemical markers (msAFP, mHCG) as possible indicators of BWS, especially in familial cases.
Subject(s)
46, XX Disorders of Sex Development/genetics , Beckwith-Wiedemann Syndrome/genetics , Congenital Abnormalities/genetics , Fetus/abnormalities , Mullerian Ducts/abnormalities , Phenotype , 46, XX Disorders of Sex Development/blood , 46, XX Disorders of Sex Development/diagnostic imaging , 46, XX Disorders of Sex Development/pathology , Adult , Beckwith-Wiedemann Syndrome/blood , Beckwith-Wiedemann Syndrome/diagnostic imaging , Beckwith-Wiedemann Syndrome/pathology , Biomarkers/blood , Chorionic Gonadotropin/blood , Congenital Abnormalities/blood , Congenital Abnormalities/diagnostic imaging , Congenital Abnormalities/pathology , Cyclin-Dependent Kinase Inhibitor p57/genetics , Female , Fetus/diagnostic imaging , Humans , Infant, Newborn , Mullerian Ducts/diagnostic imaging , Mullerian Ducts/pathology , Pregnancy , Ultrasonography, Prenatal , alpha-Fetoproteins/analysisABSTRACT
Extraskeletal Ewing sarcoma presenting as intra-abdominal or pelvic disease in adult female patients is very rare and may lead to diagnostic difficulty due to clinical and histologic overlap with Mullerian adenocarcinomas, which are far more common. We report a case of an intra-abdominal Ewing sarcoma in a postmenopausal female patient whose clinical and radiological presentation closely resembled that of peritoneal carcinomatosis. Biopsy of an omental nodule revealed numerous histologic features suggestive of a Mullerian carcinoma, including gland-like rosettes, strong, diffuse PAX8 immunoreactivity and cytokeratin expression. After excluding other differential diagnostic considerations, the possibility that this might represent an intra-abdominal Ewing sarcoma was entertained. Reverse transcriptase polymerase chain reaction testing demonstrated the presence of an EWSR1-ERG fusion transcript, confirming the diagnosis. The differential diagnostic considerations when dealing with this unusual clinical scenario and the uncommon yet important pitfall of PAX8 immunoreactivity in Ewing sarcoma are discussed.
Subject(s)
Adenosarcoma/diagnosis , Carcinoma/diagnosis , Keratins/metabolism , PAX8 Transcription Factor/metabolism , RNA-Binding Protein EWS/genetics , Sarcoma, Ewing/diagnosis , Abdomen/pathology , Adenosarcoma/pathology , Carcinoma/genetics , Carcinoma/pathology , Diagnosis, Differential , Female , Gene Fusion , Humans , Keratins/genetics , Middle Aged , Mullerian Ducts/pathology , PAX8 Transcription Factor/genetics , Peritoneal Neoplasms/pathology , Postmenopause , Sarcoma, Ewing/genetics , Sarcoma, Ewing/pathology , Transcriptional Regulator ERG/geneticsABSTRACT
STUDY OBJECTIVE: To report a new improved laparoscopic Vecchietti vaginoplasty in patients with congenital vaginal agenesis and to investigate its efficacy and safety. DESIGN: A retrospective descriptive and case-control study. SETTING: Single academic institution. PATIENTS: Women who were diagnosed with Mayer-Rokitansky-Küster-Hauster (MRKH) syndrome and underwent our new improved laparoscopic Vecchietti procedure from July 2010 to June 2019 were selected as the study group. The eligible participants had congenital vaginal agenesis with normal 46,XX karyotype and ovarian function. Age-matched, nulliparous, sexually active women were selected as the control group. INTERVENTIONS: Women with MRKH syndrome in the study group underwent the novel improved laparoscopic Vecchietti procedure. All participants in both groups were required to complete Female Sexual Function Index and Female Genital Self-Image Scale questionnaires. MEASUREMENTS AND MAIN RESULTS: The effects of our procedure, including the anatomic and functional efficacy of the neovagina, were the primary outcomes. The secondary outcomes consisted of the perioperative complications, surgical morbidities, and long-term postoperative discomfort. A total of 79 patients with MRKH syndrome underwent our new improved Vecchietti vaginoplasty, of whom 44 (55.7%) were diagnosed as Type I MRKH syndrome, whereas 35 (44.3%) were Type II MRKH syndrome. At a 30-month follow-up after surgery, an anatomic neovagina measuring 10.44 cm in length and 1.30 cm in width was achieved. All 79 patients obtained anatomic success with 92.41% of functional efficacy. Compared with 81 age-matched, nulliparous women in the control group, there was no statistical difference regardless of individual measure or total Female Sexual Function Index scores (p >.05). The Female Genital Self-Image Scale assessment showed a significantly lower score in patients undergoing the vaginoplasty (20.14 ± 3.05 vs 22.95 ± 2.12; p <.001). There were no severe perioperative complications except 1 mild bladder injury and 1 transient fever. CONCLUSION: Our novel improved laparoscopic Vecchietti vaginoplasty is a relatively safe and effective method for surgical treatment of congenital vaginal agenesis. It may be an alternative to neovagina creation for reaching satisfying anatomic and functional efficacy and improving patients' sexual function.