Efficacy of aromatase inhibitor therapy in a case with large cell calcifying Sertoli cell tumour-associated prepubertal gynaecomastia.

OBJECTIVES: Large cell calcifying Sertoli cell tumours (LCCSCTs) are one of the infrequent causes of prepubertal gynaecomastia. Most of these tumours are in the content of Peutz-Jeghers syndrome (PJS) or other familial syndromes (Carney complex). CASE PRESENTATION: Here, we report a long-term follow-up of an 8.5-year-old prepubertal boy with a diagnosis of PJS, who presented with bilateral gynaecomastia, advanced bone age and accelerated growth velocity, and were found to have bilateral multifocal testicular microcalcifications. As the findings were compatible with LCCSCT, anastrozole was initiated. Gynaecomastia completely regressed and growth velocity and pubertal development were appropriate for age during follow-up. Testicular lesions slightly increased in size. After four years of medication, anastrozole was discontinued but was restarted due to the recurrence of gynaecomastia after six months. CONCLUSIONS: Testicular tumour should be investigated in a patient with PJS who presents with prepubertal gynaecomastia. When findings are consistent with LCCSCT, aromatase inhibitors may be preferred in the treatment.

Large cell calcifying Sertoli cell tumour: a contemporary multi-institutional case series highlighting the diagnostic utility of PRKAR1A immunohistochemistry.

AIMS: Large cell calcifying Sertoli cell tumour (LCCSCT) is a rare testicular sex cord-stromal tumour that primarily affects young patients and is associated with Carney complex. We sought to characterise the clinicopathological features of a series of LCCSCT and evaluate the diagnostic utility of PRKAR1A immunohistochemistry (IHC). METHODS AND RESULTS: The LCCSCT cohort (n = 15) had a median age of 16 years (range = 2-30 years). Four patients were known to have Carney complex. PRKAR1A IHC was performed in each case. For comparison, PRKAR1A IHC was also assessed in other sex cord-stromal tumours, including Sertoli cell tumour, not otherwise specified (SCT, NOS; n = 10), intratubular large cell hyalinising Sertoli cell tumour (n = 1) and Leydig cell tumour (n = 23). Loss of cytoplasmic PRKAR1A expression was observed in all but one LCCSCT (14 of 15; 93%). PRKAR1A expression was retained in all SCTs, NOS (10 of 10; 100%), the majority of Leydig cell tumours (22 of 23; 96%) and an intratubular large cell hyalinising Sertoli cell tumour (1 of 1; 100%). One Leydig cell tumour showed equivocal staining (multifocal weak expression). CONCLUSIONS: Overall, PRKAR1A loss is both sensitive (93%) and highly specific (97%) for the diagnosis of LCCSCT. PRKAR1A loss may aid its diagnosis, particularly in sporadic cases and those that are the first presentation of Carney complex.

Be cautious of "complex hydrocele" on ultrasound in young men.

Hydrocele is the most common benign cause of painless scrotal enlargement and only very rarely can be reactive to an underlying testicular tumor. We present the case of a healthy young man, complaining of mild left scrotal discomfort and swelling. Physical examination revealed a non-tender fluctuant left scrotum and serum tumor markers were normal. Scrotal ultrasonography (US) showed a normal right hemiscrotum and testicle and a fluid collection among thickened irregular septations in the left hemiscrotum, a finding which was considered as a complex hydrocele. Intraoperatively the presumed "complex hydrocele" was in fact a multicystic testicular tumor. We proceeded with orchiectomy through the scrotal incision and pathology revealed a mixed germ cell tumor of the testis consisting of cystic teratoma, in situ germ cell neoplasia unclassified (IGCNU) and Sertoli cell tumor. This is the first reported case of this type of testis tumor presenting as complex hydrocele. The aim of this case presentation is to underline the need for an accurate preoperative diagnosis in cases of suspected scrotal pathology in young males.

Mayer-Rokitansky-Küster-Hauser Syndrome With Bilateral Ovarian Sertoli Cell Tumors: Review of the Literature and Report of a Rare Case.

BACKGROUND: Patients with Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome are infertile secondary to hypoplasia or complete agenesis of the uterus, yet they remain at risk of primary neoplasms of the ovaries because embryologically the uterus and ovaries develop via separate mechanisms. CASE: A 72-year-old nulliparous woman with a history of primary amenorrhea underwent an exploratory laparotomy for a suspected uterine fibroid. In addition to the pelvic mass, the patient was found to have findings consistent with MRKH syndrome. Postoperative pathological examination demonstrated bilateral ovarian Sertoli cell tumors. CONCLUSIONS: The case presented is unique in that 2 rare pathologies, bilateral Sertoli cell tumors of the ovary and MRKH syndrome, developed concomitantly in the same patient.

Intratubular large cell hyalinizing Sertoli cell tumor of the testis presenting with prepubertal gynecomastia: a case report.

Intratubular large cell hyalinizing Sertoli cell neoplasia (ITLCHSCN) resulting from Sertoli cells of the testis are mainly reported in young adults and these are rarely seen in childhood. The most common presenting symptoms of the patients diagnosed with ITLCHSCN are gynecomastia, enlargement in the testicles, increase in growth velocity, and advanced bone age. Symptoms are basically resulting from increased aromatase enzyme activity in Sertoli cells. In this case report, an eight-and-a-half-year-old case presenting with complaint of bilateral gynecomastia since two years, showing no endocrine abnormality in laboratory during two years of follow-up, determined to have progression in bilateral gynecomastia, increase in testicular volumes, advanced bone age, increase in growth velocity in the clinical follow-up, and diagnosed with ITLCHSCN after testis biopsy was presented.

Response to Anastrozole Treatment in a Case with Peutz-Jeghers Syndrome and a Large Cell Calcifying Sertoli Cell Tumor.

Peutz-Jeghers syndrome (PJS) is inherited as an autosomal dominant trait characterized by multiple gastrointestinal hamartomatous polyps, mucocutaneous pigmentation, and an increased risk of neoplasm. Large-cell calcifying Sertoli cell tumor (LCCSCT) is a kind of sex cord-stromal tumor which may co-exist with PJS and which is characterized radiologically by calcification foci within the testes. Surgical treatment options for this tumor range from testis-preserving surgery to radical orchiectomy. Not with standing this invasive approach, recently, there are some case reports demonstrating the efficacy of aromatase inhibitors in avoiding orchiectomy and its associated complications. In this paper, we have presented a LCCSCT case diagnosed in a boy with PJS and his response to anastrozole treatment.

Sertoli cell tumor arising in a cryptorchid testis presenting as a content of inguinal hernial sac.

Sertoli cell tumors (SCTs) are rare tumors accounting for <1% of all testicular tumors. Here, we report a rare case of SCT in a 60-year-old man presenting as a painless swelling in the right groin since childhood. Clinically, he presented with right-sided inguinal hernia with absence of the right testis. He had normal left testis and had no gynecomastia or infertility. The specimen of hernial sac showed testis with a 1.6 cm × 1.5 cm nodular mass having gray tan-cut surface. Histopathologically, the testis showed atrophy and the nodular portion showed tumor cells arranged in tubular and microcystic pattern, with no solid pattern or necrosis. The diagnosis of SCT was confirmed with immunohistochemical staining for inhibin which showed fine granular cytoplasmic positivity. Cryptorchid testis having SCT and presenting as a content of inguinal hernia is a rare occurrence.

Complete androgen insensitivity syndrome with concomitant seminoma and Sertoli cell adenoma: an unusual combination.

Androgen insensitivity syndrome is a rare disorder of sex development and its clinical manifestations vary from subtle male infertility to an overt complete androgen insensitivity syndrome (CAIS) with a female phenotype. CAIS is often diagnosed at puberty or in adolescence during investigation for primary amenorrhoea. Undiagnosed patients have an increased risk of development of malignancy in the harboured testes. Inguinal hernia is the commonest mode of presentation of CAIS in childhood and various screening methods are available during the initial herniorrhaphy procedure. Controversy exists in the need to screen and the methods of screening in all cases of premenstrual girls with inguinal hernia. Abnormal observation in a suspicious case requires karyotyping for confirmation. We describe a case of CAIS with simultaneous presence of seminoma and a Sertoli cell adenoma in a 17-year-old patient who had a history of surgery for inguinal hernia at age of 5 years.

A CASE OF AN AROMATASE-PRODUCING SERTOLI CELL TUMOR PRESENTING WITH GYNECOMASTIA.

A 64-year-old man had complained of a left scrotal mass and gynecomastia since June 2012. A left testicular tumor was suspected and the patient was referred to our department in December 2013. He presented with bilateral gynecomastia and a painless left scrotal mass that was firm, smooth surfaced, and the size of large hen's egg. Levels of markers of testicular germ cell tumors were all within normal range. Endocrinological examination revealed a marked elevation in serum estradiol (E2) level. The patient underwent high inguinal orchiectomy in December 2013.The pathological diagnosis was a Sertoli cell tumor of the left testis. Immunohistochemistry revealed the expression of aromatase synthesis; we speculated that this E2 production by the tumor caused the gynecomastia.Serum E2 level normalized after the orchiectomy. Owing to the diagnosis of malignancy, retroperitoneal lymph node dissection was performed in January 2014. No lymph node metastasis was found in the specimen. The gynecomastia improved gradually, and the patient has been free of disease since the surgery.

[Testicular nodules of infertile men and contrast enhanced ultrasonography: preliminary study]. / Nodules testiculaires de l'homme infertile et échographie de contraste: étude préliminaire.

INTRODUCTION: The incidence of testicular nodules discovered during infertility evaluation is increasing. These nodules are suspicious of malignancy. There is no paraclinical examination which allows histological orientation to these nodules. The recommendations propose priority treatment by total orchidectomy. PATIENTS AND METHODS: Through a retrospective cohort study of infertile patients, our goal is to study the enhancement of testicular nodules after injection of ultrasound contrast. The secondary objective is to determine whether CEUS may argue in favor of conservative treatment. From june 2010 to march 2013, 24 patients had underwent ultrasound contrast study of abnormal testicular parenchyma detected prior to infertility evaluation carried ultrasound. The characteristics of ultrasound enhancement were correlated with the pathological findings of surgical patients and proposed treatments (surgery or surveillance). RESULTS: Fifteen patients were followed up, 9 were operated (7 partial orchidectomies, 2 total orchidectomies). Histological analysis found four Leydig cell tumors, 2 Sertoli cell tumors and 3 seminomas. No adverse changes were noted during the follow-up. This study showed a typical semiology of early, intense and homogeneous enhancement with a phenomenon of wash in 100% of Leydig cell tumors. All Leydig cell tumors have been treated by partial orchidectomy. Seminomas have intense enhancement in 100% of cases. There was a phenomenon of wash in 2 out of 3 cases. When a wash in was described, it was always described as heterogeneous. All seminomas were finally treated by total orchidectomy. The sensitivity and positive predictive value of ultrasound intense enhancement for the diagnosis of testicular cancer was 89% (Se) and 80% (PPV). CONCLUSION: There is a semiology of ultrasound enhancement of testicular nodules with features that can guide in favor of a malignant tumor, seminoma or Leydig cell tumor. If a prospective study was undertaken, these arrangements could guide us to treatments promoting preservation of the testicular parenchyma.

Adenoma de células de Sertoli bilateral en paciente con síndrome de insensibilidad a los andrógenos / Bilateral Sertoli cell adenoma in a patient with androgen insensitivity syndrome

El síndrome de insensibilidad a los andrógenos se caracteriza por la presencia de fenotipo femenino, gónadas masculinas y cariotipo 46,XY. Es la causa más común de seudohermafroditismo masculino y la tercera causa más frecuente de amenorrea primaria, después de la disgenesia gonadal y la ausencia congénita de vagina. Es una entidad cuya importancia radica en su diagnóstico precoz en la pubertad por el riesgo de desarrollo de tumoraciones testiculares. En este artículo se presenta un caso de diagnóstico tardío de síndrome de insensibilidad a los andrógenos asociado a adenoma de células de Sertoli (AU)

Androgen insensitivity syndrome is characterized by the presence of a female phenotype, masculine gonads, and 46,XY karyotype. This syndrome is the most common cause of masculine pseudohermaphroditism and is the third most frequent cause of primary amenorrhea after gonadal dysgenesis and congenital absence of the vagina. The importance of this entity lies in its early diagnosis in puberty because of the risk of testicular tumors. In this article, we present a case of late diagnosis of androgen insensitivity syndrome related to Sertoli cell adenoma (AU)

Use of aromatase inhibitors in large cell calcifying sertoli cell tumors: effects on gynecomastia, growth velocity, and bone age.

CONTEXT: Large cell calcifying Sertoli cell tumors (LCCSCT) present in isolation or, especially in children, in association with Carney Complex (CNC) or Peutz-Jeghers Syndrome (PJS). These tumors overexpress aromatase (CYP19A1), which leads to increased conversion of delta-4-androstenedione to estrone and testosterone to estradiol. Prepubertal boys may present with growth acceleration, advanced bone age, and gynecomastia. OBJECTIVE: To investigate the outcomes of aromatase inhibitor therapy (AIT) in prepubertal boys with LCCSCTs. DESIGN: Case series of a very rare tumor and chart review of cases treated at other institutions. SETTING: Tertiary care and referral center. PATIENTS: Six boys, five with PJS and one with CNC, were referred to the National Institutes of Health for treatment of LCCSCT. All patients had gynecomastia, testicular enlargement, and advanced bone ages, and were being treated by their referring physicians with AIT. INTERVENTIONS: Patients were treated for a total of 6-60 months on AIT. MAIN OUTCOME MEASURES: Height, breast tissue mass, and testicular size were all followed; physical examination, scrotal ultrasounds, and bone ages were obtained, and hormonal concentrations and tumor markers were measured. RESULTS: Tumor markers were negative. All patients had decreases in breast tissue while on therapy. Height percentiles declined, and predicted adult height moved closer to midparental height as bone age advancement slowed. Testicular enlargement stabilized until entry into central puberty. Only one patient required unilateral orchiectomy. CONCLUSIONS: Patients with LCCSCT benefit from AIT with reduction and/or elimination of gynecomastia and slowing of linear growth and bone age advancement. Further study of long-term outcomes and safety monitoring are needed but these preliminary data suggest that mammoplasty and/or orchiectomy may be foregone in light of the availability of medical therapy.

Bilateral sertoli and interstitial cell tumours in abdominal testes of a goat with polled intersex syndrome (PIS).

An 8-year-old, mixed breed, polled goat was presented for evaluation of male-like behaviour. Clinical findings included clitoromegaly, a heavily muscled neck, pronounced beard, and erect dorsal guard hairs, which are phenotypic characteristics commonly observed in intersex animals. Transrectal ultrasonography revealed the presence of two abdominal masses caudolateral to the uterine horns. Serum concentration of estradiol was elevated. Genetic evaluation was compatible with polled intersex syndrome defined by an XX karyotype without a Y chromosome or SRY gene. Based on gross and histologic evaluation, the abdominal masses were determined to be intra-abdominal testes, each of which was effaced by Sertoli cell and interstitial (Leydig) cell tumours. The Sertoli cell tumours (SCTs) represented two unique histologic patterns. Regardless of pattern, neoplastic Sertoli cells were consistently lipid laden and positive for vimentin. Interstitial cell tumours (ICTs) were negative for vimentin. Clinical and histopathologic findings suggest that prolonged exposure to steroids secreted by neoplastic Sertoli cells contributed to virilization. In addition, results from immunohistochemistry indicated that vimentin may be a valuable immunodiagnostic tool for differentiation between interstitial and Sertoli cell tumours in goats.

Recurrent right ventricular cardiac myxoma in a patient with Carney complex: a case report.

INTRODUCTION: Carney complex is a multiple neoplasia syndrome involving cardiac, endocrine, neural and cutaneous tumors with a variety of pigmented skin lesions. It has an autosomal dominant mode of inheritance. Approximately 7% of cardiac myxomas are related to the Carney complex. Myxomas that occur as part of the Carney complex affect both sexes with equal frequency. Cardiac myxomas with Carney complex are reported mostly in the left side of the heart and are less common on the right side. As per our review, this is the first reported case of Carney complex with right ventricle cardiac myxoma. CASE PRESENTATION: We present a rare case of recurrent cardiac myxoma in a patient later diagnosed to have Carney complex. A 46-year-old Caucasian man with a history of thyroid hyperplasia came to out-patient cardiology department with new onset atrial fibrillation. A transthoracic echocardiogram revealed a right ventricular mass attached to his interventricular septum, which was later seen on a transesophageal echocardiogram and cardiac magnetic resonance imaging. He underwent resection of the ventricular mass which on pathology revealed myxoma. He later developed skin lesions, pituitary adenoma and Sertoli cell tumor suggesting Carney complex. Two years later he developed a new mass within his right atrium which was later resected. CONCLUSIONS: Carney complex is a rare autosomal dominant disease with variable penetrance. Since it involves multiple organs, patients diagnosed with Carney complex should undergo serial endocrine workup, neural assessments, echocardiograms and testicular ultrasounds. Of the total number of cases of Carney complex, 65% are linked to PRKAR1A gene mutation. It is important for clinicians to be cognizant of a link between cardiac myxoma and Carney complex. The use of multi-imaging modalities allows better delineation of the mass before planned resection. Carney complex-related cardiac myxoma comprises 7% of all cardiac myxomas. Right ventricular cardiac myxomas are rare. This case report is the first to describe right ventricular myxoma with Carney complex.

Evaluation of anti-Müllerian hormone in a dog with a Sertoli cell tumour.

BACKGROUND: Testicular tumours are common in elderly male dogs, and Sertoli cell tumours (SCTs) are among the most common. An increase in blood estradiol concentration is often seen in canine SCTs, but such measurements do not necessarily correlate with the clinical signs. CASE REPORT: A 6-year-old male Pembroke Welsh corgi was referred for nonpruritic alopecia. Clinical examination revealed cryptorchidism of the right testicle, and blood tests showed an increased estradiol concentration. The cryptorchid testis was removed by laparotomy, and SCT was diagnosed histologically. An enzyme-linked immunosorbent assay kit designed to measure human anti-Müllerian hormone (AMH) revealed a very high preoperative serum AMH concentration, which decreased after surgery. The serum AMH concentrations of two intact healthy control male dogs were lower than that of the dog with the SCT before treatment but higher than thoseof two healthy castrated male dogs. CONCLUSIONS AND CLINICAL IMPORTANCE: Canine serum AMH concentrations, as measured by a human AMH enzyme-linked immunosorbent assay, may be useful as a marker for canine SCT.

Sertolioma metastático em cão: relato de caso

Tumores da genitália de machos só não são mais incidentes que ostumores cutâneos. Os tumores testiculares são raros na maioria das espéciesdomésticas, ocorrendo com maior frequência nos cães. O Sertolioma está entre astrês mais frequentes neoplasias testiculares de cães, ao lado de tumores dascélulas de Leydig e seminomas. Vários fatores podem influenciar odesenvolvimento de tumores testiculares no cão, incluindo criptorquidismo, idade,raça e exposição a fatores cancerígenos. Há uma associação significativa entrecriptorquidismo e o desenvolvimento de tumores de células de Sertoli eseminomas. A maioria dos cães com tumores testiculares são assintomáticos, e aneoplasia testicular é geralmente um achado acidental. Os tumores das células deSertoli são comumente localmente invasivos e raramente metastáticos, mas sabeseque os tumores intra-abdominais possuem maior índice metastático. Estetrabalho visa relatar um caso de tumor das células de Sertoli com metástase emrim esquerdo em um cão SRD de 7 anos, criptorquida bilateral, submetido aorquiectomia e nefrectomia esquerda, e posterior tratamento quimioterápico comdoses alternadas de carboplatina e doxorrubicina , e até o presente momento seapresentando em completa remissão.

Tumors of male genitalia are not only more incidents than skin tumors.Testicular tumors are rare in most domestic species, occurring more frequently indogs. The Sertolioma is among the three most frequent testicular neoplasms indogs, besides Leydig cell tumors and seminomas. Several factors may influencethe development of testicular tumors in dogs, including cryptorchidism, age, raceand exposure to carcinogenic factors. There is a significant association betweencryptorchidism and tumor development of Sertoli cells and seminomas. Most dogswith testicular tumors are asymptomatic, and testicular cancer is usually anincidental finding. The Sertoli cell tumors are usually locally invasive and rarelymetastatic, but it is known that the intra-abdominal tumors have a higher metastaticrate. This paper describes a case of Sertoli cell tumor with metastasis in the leftkidney in a seven years old, male, mongrel dog, bilateral cryptorchid , submitted toorchiectomy and left nephrectomy and subsequent chemotherapy with alternatingdoses of doxorubicin and carboplatin every 21 days, and until now performing incomplete remission.

Bilateral Sertoli cell tumors of the testis-a likely new extracolonic manifestation of familial adenomatous polyposis.

Testicular Sertoli cell tumors are rare and usually sporadic and unifocal. The large cell calcifying Sertoli cell tumor variant is known to be associated with Carney and Peutz-Jeghers syndromes and can be bilateral in these patient populations. There has been no documented association of Sertoli cell tumor with familial adenomatous polyposis (FAP) in the literature. The case presented is a bilateral Sertoli cell tumor occurring in a 34-year-old patient with FAP. The tumor had a conventional Sertoli cell tumor morphology, but with different morphology in the left and right sites. Beta-catenin immunostain showed strong nuclear reactivity in the tumor cells but not the nonneoplastic Sertoli cells. The presence of bilaterality as well as overexpression of beta-catenin by this tumor supports an association of the development of Sertoli cell tumor with the patient's FAP syndrome and adenomatous polyposis coli inactivation.

Sertoli cell tumor and gonadoblastoma in an untreated 29-year-old 46,XY phenotypic male with Frasier syndrome carrying a WT1 IVS9+4C>T mutation.

OBJECTIVE: Frasier syndrome (FS) phenotype in 46,XY patients usually consists of female external genitalia, gonadal dysgenesis, high risk of gonadoblastoma and the development of end stage renal failure usually in the second decade of life. FS is caused by heterozygous de novo intronic splice site mutations of the Wilms' tumor suppressor gene 1 (WT1), although a few cases with typical exonic WT1 Denys-Drash mutations that resemble an FS phenotype have been described. The aim of this study was to present further data on the spectrum of FS phenotypes through the evaluation of a 29-year-old patient with a predominantly male phenotype and coexistence of Sertoli cell tumor and gonadoblastoma. RESULTS: Genetic analysis using standard methods for DNA sequencing confirmed FS due to a WT1 gene mutation, IVS9+4C>T. CONCLUSIONS: This very rare case illustrates the natural course of FS over many years due to the neglect by the patient to address his need for follow-up, while adding further data on the spectrum of FS phenotypes associated with IVS9+4 C>T mutations. The coexistence of the rare Sertoli cell tumor and gonadoblastoma emphasizes that early clinical recognition and molecular identification facilitates appropriate patient management, especially with respect to the high risk of gonadal malignancy.