Mixed Gonadal Dysgenesis (45 X0/46 XV Mosaicism): A case report

@#Disorders of sexual development (DSD) defined as congenital conditions associated with atypical development of anatomical, gonadal or chromosomal sex, is a rare condition that may present with ambiguous genitalia. Included in the varied classes of DSD is mixed gonadal dysgenesis which is known to be due to mosaicism, a chromosomal aberration. Mosaic individuals may have concerns on growth, hormone balance, gonadal development, sex of rearing and fertility. This case report presents an 18-year old student who presented with primary amenorrhea, delayed secondary sexual characteristics and phenotypic features of Turner syndrome who, on chromosomal analysis revealed 45X0/46XY mosaicism. The patient underwent operative laparoscopy with bilateral gonadectomy on the basis of the increased risk of development of gonadal malignancy in phenotypic females with Y-chromosome material. Histopathological analysis revealed bilateral streak gonads. Hormone replacement therapy was then initiated for the induction of secondary female sex characteristics, as treatment for estrogen deficiency, for the induction of pubertal growth spurt and for optimization of bone mineral accumulation. Management of disorders of sexual development is challenging, thus the need for a multidisciplinary approach involving experts in endocrinology, gynecology, psychology and genetics.

45,X/46,XY Mosaicism in an 18-year-old girl with primary Amenorrhea: A case report / Journal of the ASEAN Federation of Endocrine Societies

@#45,X/46,XY mosaicism is a rare disorder with a wide heterogeneity in its manifestations. An 18-year-old girl was referred to the endocrine clinic for investigation of her primary amenorrhea. Clinical examination was unremarkable. Hormonal profile was consistent with primary ovarian insufficiency and human chorionic gonadotropin (hCG) stimulation did not show evidence of active testicular tissue. Karyotyping studies by G-banding revealed a 45,X/46,XY karyotype. She was diagnosed with mosaic Turner syndrome with Y chromosomal material and investigation was performed to identify the presence of male gonads due to the risk of gonadal malignancy. Magnetic resonance imaging (MRI) of the pelvis did not show evidence of gonads. Laparoscopic exploration was proposed but the patient and parents refused opting for conservative management. This case highlights the challenges in the management of this rare condition.

Pubertal outcomes and sex of rearing of patients with ovotesticular disorder of sex development and mixed gonadal dysgenesis

PURPOSE: Patients with ovotesticular disorder of sex development (DSD) and mixed gonadal dysgenesis (MGD) usually present with asymmetric gonads and have wide phenotypic variations in internal and external genitalia. The differential diagnosis of these conditions is based on karyotype and pathological findings of the gonads. This study investigated the clinical features at presentation, karyotype, sex of rearing, and pubertal outcomes of patients with ovotesticular DSD and MGD.METHODS: The study comprised 23 patients with DSD who presented with asymmetric gonads. The presenting features, karyotype, sex of rearing, and pubertal outcomes were reviewed retrospectively.RESULTS: All 23 patients presented with ambiguous genitalia at a median age of 1 month (range, 1 day–1.6 years). Müllerian duct remnants were identified in 15 of 23 patients (65.2%). Fourteen patients were diagnosed with ovotesticular DSD, whereas the other 9 were diagnosed with MGD. Eight of 14 patients (57.1%) with ovotesticular DSD were raised as males, while 7 of 9 patients with MGD (77.8%) were assigned as males. One male-assigned patient with ovotesticular DSD changed to female sex at age 20 years.CONCLUSION: Patients with ovotesticular DSD and MGD manifest overlapping clinical presentations and hormonal profiles. It is difficult to determine the sex of rearing and predict long-term pubertal outcomes. Therefore, long-term follow-up is required to monitor spontaneous puberty, sex outcome, and urological and gynecological complications.

Early development of a gonadal tumor in a patient with mixed gonadal dysgenesis

SUMMARY A gonadal tumor was diagnosed in the first months of life in a patient with genital ambiguity, a 45,X/46,XY karyotype, and mixed gonadal dysgenesis. Gonadal biopsies at the age of 3 months revealed dysgenetic testes and a gonadoblastoma on the right testis. Even though gonadal tumors are rare in childhood, this case indicates that prophylactic removal of dysgenetic gonads should be performed as early as possible, especially when the female sex is assigned to a patient with a Y-chromosome sequence.

Clinical and genetic analysis for a patient with 45, X/46, X, Yqh- and mixed gonadal dysgenesis / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the clinical and genetic characteristics of a patient with mixed gonadal dysgenesis.</p><p><b>METHODS</b>Clinical data was collected. The patient was subjected for serum hormone testing and G-banding chromosomal analysis. Sex-determining region of Y-chromosome (SRY) gene and azoospermia factor (AZF) a, b, c regions were analyzed with multiple polymerase chain reaction (PCR) and whole gene sequencing.</p><p><b>RESULTS</b>All serum hormone testing were normal. The karyotype of the patient was 45,X/46,X,Yqh-. PCR has proven the presence of SRY, ZFY and AZFa, and deletion of AZFb and AZFc regions. No mutation was detected in the sequence of the SRY gene. Abdominal computerized tomography has detected a huge mass in the pelvic cavity, which was positive for PLAP and CD117 on immunohistochemistry stain.</p><p><b>CONCLUSION</b>Based on clinical data and result of genetic testing, the patient was diagnosed with mixed gonadal dysgenesis. Pathological and immunohistochemistry analysis of the transformed gland has confirmed the diagnosis of seminoma. For patient with a karyotype of 45,X/46,X,Yqh-, the risk of seminoma may be related with the presence of SRY gene.</p>

Disgenesia gonadal mixta como forma de presentación de un desorden de la diferenciación sexual de causa cromosómica / Mixed gonadal dysgenesis as a form of presentation of sex differentiation disorder of chromosomal origin

La diferenciación sexual es un proceso genéticamente determinado y controlado, que puede ser alterado por diferentes tipos de mutaciones genéticas, o por el efecto de hormonas u otros disruptores ambientales que actúan sobre el embrión, resultando en la formación de genitales externos que no se corresponden con el sexo genético y con los genitales internos. La disgenesia gonadal mixta clasifica en los desórdenes de la diferenciación sexual de causa cromosómica. Se describe un paciente de un año de edad que es atendido en el Hospital Pediátrico “Juan Manuel Márquez”, por presentar genitales externos atípicos. El diagnóstico del paciente fue de disgenesia gonadal mixta, y se realizó con los complementarios siguientes: ecografía ginecológica, estudios hormonales y cariotipo. El tratamiento instaurado inicialmente, fue quirúrgico en dos tiempos operatorios, y el seguimiento hormonal hasta la pubertad (14 años), cuando se inició terapia de reemplazo hormonal según lo establecido por la edad de la paciente.

Sex differentiation is a genetically determined and controlled process that may be altered by various types of genetic mutations or by the effect of hormones or other environmental disruptors acting upon the embryo. The result is the formation of external genitalia that does not match with the genetic sex and the internal genitalia. Mixed gonadal dysgenesis is classified into the sexual differentiation disorders of chromosomal cause. Here is a one-year old child, who was seen at “Juan Manuel Marquez” pediatric hospital since he presented with atypical external genitalia. The diagnosis was mixed gonadal dysgenesis, based on supplementary tests like gynecological echography, hormone studies and karyotype. The initial treatment was surgical in two surgical times, and the hormonal follow-up lasted till puberty (14 years) when the hormone replacement therapy started according to the indications for the patient's age.

Mixed gonadal dysgenesis in 45,X Turner syndrome with SRY gene

Turner syndrome is the most common chromosomal disorder in girls. Various phenotypic features show depending upon karyotype from normal female through ambiguous genitalia to male. Usually, Turner girls containing 45,X/46,XY mosaicism, or sex-determining region Y (SRY) gene may have mixed gonadal dysgenesis with various external sexual differentiation. We experienced a short statured 45,X Turner girl with normal external genitalia. Because SRY gene was positive, laparoscopic gonadectomy was performed. The dysgenetic gonads revealed bilateral ovotesticular tissues. The authors report a mixed gonadal dysgenesis case found in clinical 45,X Turner patient with positive SRY gene. Screening for SRY gene should be done even the karyotype is 45,X monosomy and external genitalia is normal.

Uso da FISH em mucosa oral para investigação de mosaicismo com linhagem 45,X: estudo com homens saudáveis e pacientes com distúrbios da diferenciação do sexo / The use of FISH on buccal smear to investigate mosaicism with a 45,X cell line: study on healthy men and patients with disorders of sex development

Objetivo: Verificar se a hibridização in situ por fluorescência (FISH) em células de mucosa oral poderia ser empregada para detectar criptomosaicismo com linhagem 45,X em pacientes 46,XY. Sujeitos e métodos: Amostra de 19 jovens saudáveis 46,XY e cinco pacientes com distúrbios da diferenciação do sexo (DDS), quatro 45,X/46,XY e um 46,XY. FISH com sondas específicas para X e Y em núcleos interfásicos de linfócitos e mucosa oral para investigar a proporção de núcleos contendo apenas o sinal do cromossomo X. Resultados: A frequência de núcleos contendo apenas o sinal do X nos dois tecidos dos homens saudáveis não diferiu (p = 0,69). Em todos os pacientes com DDS essa frequência foi significativamente maior, e também não houve diferença entre os dois tecidos (p = 0,38). Conclusões: A investigação de mosaicismo com linhagem 45,X em pacientes com DDS 46,XY ou esterilidade pode ser feita por FISH diretamente em células de mucosa oral. .

Objective: To verify whether fluorescence in situ hybridization (FISH) of cells from the buccal epithelium could be employed to detect cryptomosaicism with a 45,X lineage in 46,XY patients. Subjects and methods: Samples of nineteen 46,XY healthy young men and five patients with disorders of sex development (DSD), four 45,X/46,XY and one 46,XY were used. FISH analysis with X and Y specific probes on interphase nuclei from blood lymphocytes and buccal epithelium were analyzed to investigate the proportion of nuclei containing only the signal of the X chromosome. Results: The frequency of nuclei containing only the X signal in the two tissues of healthy men did not differ (p = 0.69). In all patients with DSD this frequency was significantly higher, and there was no difference between the two tissues (p = 0.38), either. Conclusions: Investigation of mosaicism with a 45,X cell line in patients with 46,XY DSD or sterility can be done by FISH directly using cells from the buccal epithelium. .

The use of fluorescence in situ hybridization in the diagnosis of hidden mosaicism: apropos of three cases of sex chromosome anomalies / O uso da hibridação in situ com fluorescência no diagnóstico de mosaicismo oculto: a propósito de três casos de anomalias de cromossomos sexuais

FISH has been used as a complement to classical cytogenetics in the detection of mosaicism in sex chromosome anomalies. The aim of this study is to describe three cases in which the final diagnosis could only be achieved by FISH. Case 1 was an 8-year-old 46,XY girl with normal female genitalia referred to our service because of short stature. FISH analysis of lymphocytes with probes for the X and Y centromeres identified a 45,X/46,X,idic(Y) constitution, and established the diagnosis of Turner syndrome. Case 2 was a 21-month-old 46,XY boy with genital ambiguity (penile hypospadias, right testis, and left streak gonad). FISH analysis of lymphocytes and buccal smear identified a 45,X/46,XY karyotype, leading to diagnosis of mixed gonadal dysgenesis. Case 3 was a 47,XYY 19-year-old boy with delayed neuromotor development, learning disabilities, psychological problems, tall stature, small testes, elevated gonadotropins, and azoospermia. FISH analysis of lymphocytes and buccal smear identified a 47,XYY/48,XXYY constitution. Cases 1 and 2 illustrate the phenotypic variability of the 45,X/46,XY mosaicism, and the importance of detection of the 45,X cell line for proper management and follow-up. In case 3, abnormal gonadal function could be explained by the 48,XXYY cell line. The use of FISH in clinical practice is particularly relevant when classical cytogenetic analysis yields normal or uncertain results in patients with features of sex chromosome aneuploidy. Arq Bras Endocrinol Metab. 2012;56(8):545-51.

FISH tem sido usado como um complemento para a citogenética clássica na detecção de mosaicismo em anomalias de cromossomos sexuais. O objetivo deste trabalho é descrever três casos nos quais o diagnóstico final só foi obtido por meio de FISH. O caso 1 é uma menina de 8 anos, 46,XY, com genitália feminina normal, encaminhada ao nosso setor devido à baixa estatura. A análise de linfócitos por FISH com sondas centroméricas de X e Y identificou a constituição 45,X/46,X,idic(Y) e estabeleceu o diagnóstico de síndrome de Turner. O caso 2 é um menino de 21 meses, 46,XY, com ambiguidade genital (hipospadia peniana, testículo à direita e gônada disgenética à esquerda). FISH de linfócitos e mucosa oral identificou o cariótipo 45,X/46,XY, levando ao diagnóstico de disgenesia gonadal mista. O caso 3 é um rapaz de 19 anos, 47,XYY, com atraso de desenvolvimento neuromotor, dificuldade de aprendizado, problemas psicológicos, alta estatura, testículos pequenos, gonadotrofinas elevadas e azoospermia. FISH de linfócitos e mucosa oral identificou a constituição 47,XYY/48,XXYY. Os casos 1 e 2 ilustram a variabilidade fenotípica do mosaico 45,X/46,XY e a importância da detecção da linhagem 45,X na avaliação e na condução dos casos. No caso 3, a função gonadal anormal pôde ser explicada pela linhagem 48,XXYY. O uso de FISH na prática clínica é particularmente relevante quando a análise citogenética clássica traz resultados normais ou incertos em pacientes com quadro sugestivo de uma aneuploidia de cromossomos sexuais. Arq Bras Endocrinol Metab. 2012;56(8):545-51.

Neoplasias em gônadas disgenéticas / Neoplasms in dysgenetic gonadal

Conceitualmente, as gônadas disgenéticas são gônadas que não sofreram uma completa diferenciação. Em vista disso, constituem parte de uma ampla gama de entidades clínicas possuidoras de fenótipos e de genótipos diversos. Seus cariótipos contêm o cromossomo Y ou seus fragmentos, ou raramente não os contêm. Essas alterações geram maior risco para a ocorrência de neoplasias nessas gônadas. Na sequência deste estudo apresentamos as neoplasias mais comumente associadas aos diversos tipos de disgenesias gonadais. A neoplasia mais comum é o gonadoblastoma e outros como os disgerminomas e os tumores do seio endodérmico também podem estar associados. A detecção dessas anormalidades de modo precoce é o que nos motivou para a presente revisão

By definition, dysgenetic gonads are those that did not undergo a complete differentiation. They make up a vast array of clinical entities, having different phenotypes and genotypes. Their kariotypes contain the Y chromosome or fragments of it, and, in rare cases, do not contain it. Such alterations generate greater potential for the occurrence of neoplasms in such gonads. This study presents neoplasms which are most commonly associated with several types of gonadal dysgenesis. The most common neoplasia is gonadoblastoma and others like disgerminoma or yolk sac tumors may be associated. The early detection of such potential is the reason for this review

46,XY and 45,X/46,XY testicular dysgenesis: similar gonadal and genital phenotype, different prognosis / Disgenesias testiculares 46,XY e 45,X/46,XY: fenótipo genital e gonadal semelhante, prognóstico distinto

The objective of this study was to describe the change in diagnosis and prognosis of a child with testicular dysgenesis and 46,XY karyotype after detection of a 45,X cell line and to discuss the difficulties caused by the terms mixed gonadal dysgenesis (MGD) and XY partial gonadal dysgenesis (XYPGD). One case was reported including clinical and laboratory findings of a child of 41-day-old infant with 1.3-cm phallus, penoscrotal hypospadias and left prepubertal testis. Karyotype 46,XY (16 cells), normal hormone levels. Right streak gonad, epididymis and müllerian remnants were removed; initial diagnosis was XYPGD. Persistent growth retardation led to further cytogenetic analysis (50 cells) and detection of a 45,X cell line. Detection of a 45,X lineage changed both the diagnosis to MGD and also the prognosis.The number of cells analyzed in karyotyping is critical. Use of MGD and XYPGD to designate both a histological picture and a syndromic diagnosis, results in lack of emphasis on clinical differences between 46,XY and 45,X/46,XY subjects.

O objetivo deste trabalho foi descrever a mudança no diagnóstico e no prognóstico de criança com disgenesia testicular e cariótipo 46,XY após detecção de linhagem 45,X e discutir as dificuldades causadas pelas denominações disgenesia gonadal mista (DGM) e disgenesia gonadal parcial XY (DGPXY). Relatou-se um caso incluindo achados clínicos e laboratoriais de uma criança de 41 dias com falo de 1,3 cm, hipospadia penoescrotal e testículo pré-puberal à esquerda. Cariótipo 46,XY (16 células), níveis hormonais normais. Gônada direita (disgenética), epidídimo e remanescentes müllerianos foram removidos; o diagnóstico inicial foi DGPXY. Retardo de crescimento persistente levou à ampliação da análise citogenética (50 células) e à detecção de linhagem 45,X. A detecção de linhagem 45,X modificou o diagnóstico para DGM e também o prognóstico. No cariótipo, o número de células analisadas é crítico. O uso de DGM e DGPXY para designar tanto quadro histológico quanto diagnóstico clínico resulta em falta de ênfase nas diferenças clínicas entre indivíduos 46,XY e 45,X/46,XY.

Mosaicismo tuner 45XO/XY: diagnóstico diferencial con disgenesia gonadal mixta / Turner Mosaicism 45XO/XY: differential diagnostic with mixed gonadal dysgenesis

Se presenta el caso de una paciente de 14 años y ocho meses, referida a la consulta por presentar amenorrea, talla baja y estigmas turnerianos al examen físico. El cariotipo realizado en sangre periférica y gónadas, así como el perfil endocrinológico y el resultado histopatológico de las gónadas fueron fundamentales para establecer el diagnóstico diferencial con disgenesia gonadal mixta. Se indicó terapia de reemplazo hormonal con estrógenos equinos conjugados presentando buena evolución clínica

Mixed Gonadal Dysgenesis Mimicking True Hermaphroditism

A differential diagnosis between the true hermaphroditism (TH) and mixed gonadal dysgenesis (MGD) has important clinical implications for gender assignment and the decision for early gonadectomy; however, variable clinical and histological features frequently lead to the confusion of TH with MGD. A 17- month-old boy was presented with proximal hypospadias with chordee and right non-palpable testis in his scrotum. He also had right auricular anomaly including a separated tragus with skin tag. Left testis was well palpable in his left scrotum. Diagnostic right inguinal exploration showed Mullerian structures such as a gonad like an ovary and a fallopian tube with a uterus, which were removed. Repair of hypospadias and right auricular anomaly was also done. Following ultrasonography (USG) showed a normal looking testis in left scrotum. His chromosome was 45, XO/46, XY. We report a difficult case of mixed gonadal dysgenesis mimicking true hermaphroditism which combines ipsilateral congenital auricular anomaly.

Clinical Review of the Etiologic Factors in Patients with Aambiguous Genitalia / 대한산부인과학회잡지

OBJECTIVE: To review and evaluate the etiologic factors in patients with ambiguous genitalia METHODS: We reviewed the medical records of the patients in whom ambiguous genitalia was identified in Asan Medical Center from Jan, 1989 to Dec, 2002. Patients with isolated cryptorchidism, isolated hypospadias, or congenital fatal anomalies involving multiple organs were excluded in our series. RESULTS: A total of 58 cases were evaluated. The most common cause was congenital adrenal hyperplasia (CAH) (18 cases, 31.0%), followed by partial androgen insensitivity syndrome (AIS) (16 cases, 27.6%), true hermaphroditism (9 cases, 15.5%), and mixed gonadal dysgenesis (5 cases, 8.6%). Morphologic abnormalities observed in patients with ambiguous genitalia were hypospadias (52.5%), clitoromegaly (47.5%), palpable gonads (45.8%), bifid scrotum (23.7%), penoscrotal transposition (22%), cryptorchidism (18.6%), vaginal wall abnormality (10.2%), and M llerian remnant (3.4%). By karyotyping, 46XX, 46XY, and Y containing mosaicism were found in 24, 22, and 9 patients, respectively. All of the 18 patients with CAH were found to have 21-hydroxylase deficiency and all cases of androgen insensitivity syndrome were partial type. CONCLUSION: These findings suggest that etiologic background might be different in patients with ambiguous genitalia in Korea.

Causes and Clinical Characteristics of Patients with Abnormal Sex Differentiation and Development / 대한진단검사의학회지

BACKGROUND: Abnormal sex differentiation and development may present ambiguous genitalia in the newborn or lack of secondary sexual characteristics in puberty. A prompt and accurate diag-nosis should be established to minimize or avoid medical, psychological and social complications. The purpose of this study was to evaluate the causes and clinical characteristics of patients with abnormal sex differentiation and development. METHODS: We analyzed 35 patients with abnormal sex differentiation and development. Twenty patients had been considered or reared as males and fifteen patients as females. The diagnostic evaluation consisted of physical examination, hormonal analysis, sonogram, genitogram, gonadal biopsy and cytogenetics. RESULTS: Among the thirty-five patients, 11 patients were hypogonadism, 9 male pseudoherma-phroditism (5 hypospadia, 2 androgen insensitivity syndrome), 6 female pseudohermaphroditism (4 congenital adrenal hyperplasia), 4 micropenis, 4 congenital anomaly and 1 mixed gonadal dys-genesis. Gonadectomy was performed in patients with androgen insensitivity syndrome and mixed gonadal dysgenesis. Sex of rearing and gender assignment were all concordant with the known sex except one patient, who was previously reared as female and finally reassigned as male due to 5-alpha reductase deficiency. CONCLUSIONS: The causes of abnormal sex differentiation and development were variable. There-fore, an accurate diagnosis should be made by history, physical examination, radiologic and laboratory tests. Proper management and sex assignment are needed in accordance with the cause.

Gonadoblastoma Overgrown by Dysgerminoma in Women with 46,XX Karyotype: A Report of Two Cases

Gonadoblastoma is a neoplasm containing an intimate mixture of germ cells and elements resembling immature granulosa or Sertoli cells. It has been considered as in situ germ cell malignancy that can be overgrown by more malignant germ cell neoplasms. The tumor has been reported to almost exclusively develop in various types of gonadal maldevelopment syndromes containing the Y chromosome, such as in pure or mixed gonadal dysgenesis and, less commonly, in male hermaphroditism. However, occurrences in phenotypically and chromosomally normal, menstruating women are exceptionally rare. We report two cases of gonadoblastoma overgrown by dysgerminoma occurring in the ovaries of phenotypically and cytogenetically normal menstruating women. One of the two cases showed an area composed of granulosa cell tumor-like elements. This type of combination has been very rarely described, and exemplified that gonadoblastoma may progress to sex cord-stromal tumors as well as to the malignant germ cell tumors.

Disgenesia gonadal mixta con fórmula cromosómica 45,X/46,X, (mar): Presentación de una paciente / Mixed gonodal dysgenesis with chromosomic formula 45, X/46,X (mar): A case report

Se presentó una paciente con estigmas turnerianos y cariotipo 45,X/46,XX con diagnóstico inicial de síndrome de Turner a la que se le realizó clitoridectomía por hipertrofia del clítoris a los 8 meses de edad. Se reevaluó a los 6 años de edad y se le realizó cariotipo con técnicas de bandas G (GTG) con fórmula cromosómica de 45,X/46,X, (cromosoma marcador -mar); dicho marcador dio la impresión de una deleción del cromosoma X desde Xq13 ®Xq ter y Xp22 ®Xp ter. Se completó dicho estudio con técnica molecular de reacción en cadena de la polimerasa (PCR) y se identificó el gen SRY en el cromosoma marcador. Se realizó intervención quirúrgica por mínimo acceso y se comprobó ausencia de útero así como trompa en el lado derecho con ausencia de gónada y en el lado opuesto, testículo rudimentario; se planteó el diagnóstico de disgenesia gonadal mixta(AU)

A case of gonadoblastoma in patient with mixed gonadal dysgenesis / 대한산부인과학회잡지

Gonadoblastoma occurs almost always in association with a Y chromosome cell line, and developes in one third of patients with Mixed gonadal dysgenesis. Removing of gonads of intersex patients with the Y chromosome is very important because of the strong association of the genesis of tumor in dysgenetic gonads with the presence of a Y chromosome. But it is always possible that an XY cell line could be missed, or that a fragment from Y chromosome could have been translocated and not discovered by chromosomal analysis. PCR with Y specific probe or Southern blotting would reveal the presence of a Y or a translocated fragment. We experienced an 18-year-old woman represent with primary amenorrhea who had 45,X/46,X,+mar. Y-specific PCR revealed that the marker chromosome was drived from Y chromosome. After both gonadectomy and clitorial recession, we found the gonadoblastoma in dysgenetic testis. So we report it with brief review of literatures.

Critical Histopathologic Findings for Differential Diagnosis between True Hermaphroditism and Mixed Gonadal Dysgenesis / 대한비뇨기과학회지

PURPOSE: Differentiation of true hermaphroditism (TH), from mixed gonadal dysgenesis (MGD), in patients presenting with ambiguous genitalia and asymmetric gonad, is mandatory. However, clinical features, including chromosomal, hormonal, biochemical and radiological findings are not helpful in the differential diagnosis between these conditions, so histopathological diagnosis of the gonads is essential. We reviewed the clinicopathological features of TH and MGD to investigate the important histopathological criteria for the differential diagnosis. MATERIALS AND METHODS: The medical records of 38 patients with ambiguous genitalia were retrospectively reviewed. 8 patients had been diagnosed as TH or MGD, so their histological slides were reevaluated. We also studied the normal gonadal histology for the prenatal period in order to get basic knowledge on the histological features of premature testis and ovaries in infancy. RESULTS: To make a clear diagnosis between TH and MGD, the histological features of the ovarian compartment are important. The well-formed primordial, primary or mature follicles, with primary oocytes in TH, were distinguishable from the primitive germ cells in the ovarian-type stroma and primitive sex-cord like structures in MGD. On the contrary, the testicular compartment under both conditions was not critical for the differential diagnosis. A streaky gonadal portion should be examined to avoid missing the diagnosis of a streak-testis. CONCLUSIONS: The differential diagnosis between TH and MGD depends on the interpretation of the histological features of the gonads. For the purpose of a differential diagnosis, we have to understand the normal gonadal histology at the infantile period, and apply strict criteria to the gonads, such as testis, ovary, streak gonad and streak-testis through examination of the entire tissue.