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.

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.

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.

Large-cell calcifying Sertoli cell tumors of the testes in pediatrics.

PURPOSE OF REVIEW: The aim of this review is to describe the clinical, biochemical, radiographic, histological, and functional characteristics of large-cell calcifying Sertoli cell tumors of the testes (LCCSCTs). We describe the two main syndromes associated with these tumors: Peutz-Jeghers syndrome (PJS) caused mainly by mutations in the STK11 (aka LKB1) gene, which encodes a serine-threonine kinase, and Carney complex (CNC), which is most often caused by PRKAR1A mutations, the gene encoding regulatory subunit type 1 of protein kinase A. RECENT FINDINGS: Relatively few patients have been reported in the literature with LCCSCTs. In children they often present as prepubertal and/or peripubertal gynecomastia. Although these tumors are very rare, they occur with higher frequency among patients with PJS and CNC. Orchiectomy was often performed in the past; however, these tumors are overwhelmingly benign and, unless there are significant hormonal changes or pain and/or mass effects, there is no need for surgery. Tumors that lead to hyperestrogenemia may be treated efficiently with aromatase inhibitors; any change in appearance should prompt evaluation for malignancy. SUMMARY: The detection of LCCSCTs may point to an underlying genetic multiple neoplasia syndrome such as PJS or CNC. Surgery is rarely indicated and aromatase inhibitors constitute an effective treatment for those cases that are associated with gynecomastia and/or advanced skeletal age.

A pure Sertoli cell tumor of the ovary in a 10-year-old female.

STUDY OBJECTIVE: To document an unusual presentation of a pure Sertoli Cell tumor. DESIGN: Case report. RESULTS: We present a 10-year-old female who presented with abdominal pain and diarrhea with no symptoms of puberty. Surgical exploration revealed a metastatic pure Sertoli Cell tumor, which was treated with resection and chemotherapy. CONCLUSION: Sertoli cell tumors are rare occurrences and should be considered in the differential diagnosis for a prepubescent girl with an abdominal mass.

Surgery in infants and children with testicular and paratesticular tumours: a single centre experience over a 25-year-period.

Testicular and even more paratesticular tumours in children are rare. The aim of the study is to characterise the spectrum of these lesions with focus on the feasibility and effectiveness of testis sparing surgery. Twenty-four boys treated between 1980 and 2004 at the University Leipzig Medical Centre were evaluated. At presentation patients were between 5 months and 18 years old (median 23 months). Generally a high rate of malignant or potentially malignant tumours was observed. The majority of these tumours occurred in the first three years of age. The spectrum of testicular tumours comprised 13 germ cell tumours (6 yolk sac tumours, 6 teratomas, 1 embryonal carcinoma) and 4 sex cord stromal tumours (2 Leydig's cell, Sertoli's cell, granulosa cell). Both Leydig's cell tumours were endocrine active. Further on, we observed 3 boys with paratesticular rhabdomyosarcoma (RMS), and three with testicular and paratesticular metastases (Wilms' tumour, neuroblastoma, leukaemia). Serum alpha1-fetoprotein (AFP) was clearly elevated in 5 of 6 yolk sac tumours but remained within normal limits concerning the other entities. Human chorionic gonadotrophin was normal in all cases tested. During the observation period high inguinal orchidectomy was the surgical standard method. Dependent on tumour histology, stage and the recommended treatment schedule postoperative chemotherapy was added. Testis sparing surgery was performed in 3 boys with primary testicular tumours (2 Leydig's cell, mature cystic teratoma). Local relapses were not observed. Systemic relapses occurred in 3 cases (2 RMS, leukaemia). During a median follow up of 5 years all patients with primary testicular tumours survived event free. Meta-analysis of the recent literature revealed that testis sparing surgery is feasible and save in prepubertal boys after exclusion of a malignant tumour. If a testis sparing approach is planned, the following criteria are essential: 1. The presence of a well defined circumscribed nodule confirmed by imaging. 2. Normal levels of serum AFP and hCG. 3. The presence of sufficient healthy testicular parenchyma. However, the high rate of malignant or potentially malignant tumours suggests that high inguinal orchidectomy should remain the surgical standard of therapy.

Prepubertal gynecomastia in Peutz-Jeghers syndrome: incomplete penetrance in a familial case and management with an aromatase inhibitor.

BACKGROUND: Peutz-Jeghers syndrome (PJS) is a rare autosomal-dominant disorder characterized by multiple gastrointestinal hamartomatous polyps, mucocutaneous pigmentation and increased predisposition to various neoplasms. Endocrine manifestations in PJS include gynecomastia due to calcified Sertoli cell testicular tumors usually referred to as large-cell calcifying Sertoli cell tumors (LSCT). OBJECTIVE: To evaluate the value of endocrine markers and aromatase inhibitor treatment in children with PJS and LSCT. DESIGN AND SETTING: Familial cases, followed in a tertiary care center. PATIENTS: Two male siblings aged 7 and 9 years with PJS and LSCT. INTERVENTION: Third generation aromatase inhibitor (anastrozole) in one of the patients. MAIN OUTCOME MEASURES: Longitudinal measurements of sex-steroids, gonadotropins, Sertoli cell markers and auxological evaluation. RESULTS: The two male siblings with PJS had similar bilateral multifocal testicular calcifications and biochemical evidence of Sertoli cell dysfunction manifested by elevated plasma inhibin-alpha levels. Only one sibling had gynecomastia. Estradiol levels were normal in both. During treatment with anastrozole, estradiol levels, growth and skeletal maturation, as well as Sertoli cell markers (inhibin B, inhibin-alpha and anti-Mullerian hormone) decreased. CONCLUSIONS: Inhibin-alpha may be considered as a marker for LSCT in children with PJS, pointing to a specific defect in inhibin regulation in this condition. Moreover, the decrease in Sertoli cell markers during aromatase inhibitor treatment suggests that increased estrogen production is a primary event regulating downstream production of Sertoli cell peptides. Anastrozole is efficient in controlling the clinical features of the disease and should be proposed as an alternative to bilateral orchidectomy, which is often performed in this condition.

Sertoli cell tumor causing prepubertal gynecomastia in a boy with peutz-jeghers syndrome: the outcome of 1-year treatment with the aromatase inhibitor testolactone.

Peutz-Jeghers syndrome (PJS) is a rare disorder characterized by benign intestinal hamartomatous polyps and mucocutaneous pigmentation, and with an increased risk for intestinal and extra-intestinal neoplasms. Sertoli cell tumors in boys with PJS have been increasingly recognized as a cause of prepubertal gynecomastia. However, an association between nephrocalcinosis and PJS has not been reported before. We report on a 7.25-year-old boy with PJS, bilateral gynecomastia, Sertoli cell tumor and nephrocalcinosis, and present the outcome of 1-year treatment with the aromatase inhibitor testolactone. The patient presented with bilateral breast and testis enlargement, and mucocutaneous pigmentation. Testicular ultrasound revealed parenchymal multiple microcalcifications. Histopathological examination was consistent with Sertoli cell tumors. Nephrocalcinosis due to idiopathic renal hypercalciuria was also detected. The aromatase inhibitor testolactone was begun in an attempt to prevent acceleration in skeletal maturation. One-year treatment with testolactone reduced the breast base diameter from 7 to 3 cm, and bone age advanced 1.2 years during this period. Our case demonstrates that waiting for the effect of aromatase inhibitors on gynecomastia before making a decision for mastectomy may be a reasonable option. We also consider that the association between PJS and nephrocalcinosis may be a coincidence.

"Onco-tese": testicular sperm extraction in azoospermic cancer patients before chemotherapy-new guidelines?

OBJECTIVES: To examine the usefulness of pretreatment testicular sperm extraction because some patients have tumor-induced azoospermia. In view of the high cure rates for testicular germ cell tumors and malignant lymphomas, increasing clinical importance is attached to protecting fertility. High-dose cytostatic therapy may be expected to cause long-term infertility. Thus, the standard procedure for fertility protection is cryopreservation of ejaculated spermatozoa before therapy. METHODS: Contralateral testicular biopsies were taken from 14 azoospermic patients with malignant testicular germ cell tumors. In addition, 17 patients with malignant lymphomas underwent unilateral (n = 6) or bilateral (n = 11) testicular biopsy. The tissue specimens were cryopreserved, and the histologic workup was performed at the same time. RESULTS: Of the 14 patients with malignant testicular germ cell tumors, 6 had spermatozoa in their testicular biopsies. Sertoli cell-only syndrome was found in 5 patients, and 3 had maturation arrest without detection of spermatozoa. Successful sperm recovery was possible in 8 of the 17 patients with malignant lymphoma, 4 had Sertoli cell-only syndrome, and 5 had maturation arrest. None of the patients had evidence of secondary wound healing or treatment delay because of the testicular biopsy. CONCLUSIONS: Our results show that testicular sperm extraction is a useful technique for obtaining spermatozoa before cytotoxic therapy in azoospermic cancer patients. This procedure should be considered as an option for fertility preservation in azoospermic cancer patients, because high cumulative cytostatic doses can cause irreversible fertility alterations.

Malignant sertoli cell tumour of the testis in a child.

Very few cases of malignant Sertoli cell tumour of the testis are reported in the literature. The average age at discovery of this tumour is 39 years. Malignant Sertoli cell tumour of the testis in a child is presented, the fourth case reported in the literature. We present our case to increase awareness of this tumour in this age group, to point out the capability of Sertoli cell tumours to metastasize, and to document the remarkable initial response to combination chemotherapy, a hitherto unreported feature.

[A case of malignant Sertoli cell tumor of the testis].

A 74-year-old man consulted our hospital about a painless swelling of the right scrotal contents. Laboratory findings showed no abnormalities. A right high orchiectomy was performed. The tumor measured 4.2 X 6.0 cm in size and was yellow-white in color. Histologically, the tumor was diagnosed as a malignant Sertoli cell tumor on the basis of findings of invasion and a high mitosis rate. Combined chemotherapy was performed after the operation and no recurrence was found. The Sertoli cell tumor of the testis is a rare neoplasm, and its malignant type is extremely rare. In Japan, 7 cases have been reported, and only 2 of them have been malignant. This case is the 3rd instance malignant Sertoli cell tumor in this country.

Steroid receptors and response to hormonal and cytotoxic agents in vitro in two cases of androblastoma.

Cytosol steroid receptor contents of 2 tubular androblastomas were determined and that was correlated with the response to hormonal (tamoxifen and medroxyprogesterone acetate) and cytotoxic agents (chlorambucil, vincristine, cisplatin and etoposide) using a new in vitro method based on ATP measurement of cultured cells. Both androblastomas showed low receptor contents and no response to medroxyprogesterone acetate, tamoxifen or their combination was found. Furthermore, there was no response to chlorambucil or vincristine or their combination as well as to the combination of tamoxifen and vincristine in one tumor. The other tumor, however, showed good in vitro response to cisplatin and the combination of cisplatin and etoposide.

Hemolytic uremic syndrome in a patient on cis-platinum, vinblastine and bleomycin.

A 23-year-old woman with metastatic Sertoli-Leydig cell tumor was treated with cisplatin, vinblastine, and bleomycin. Hemolytic uremic syndrome appeared, while no evidence of residual tumor was found. Infusion of fresh frozen plasma together with aspirin and dipyridamole resulted in recovery of microangiopathic hemolytic anemia and thrombocytopenia. Renal insufficiency, however, persisted.

Recurrence of a gonadal stromal cell tumor (Sertoli Leydig cell with heterologous elements) in a teenager.

An unusual case of a moderately well-differentiated, encapsulated, Sertoli Leydig cell tumor with heterologous elements recurring 3 years after a conservative unilateral oophorectomy in a 15-year-old female is reported. This is the first case report of a metastatic Sertoli Leydig cell tumor with mucinous heterologous elements. A relative lack of uniformly accepted histological criteria of these tumors makes prognosis difficult to access. The optimal therapy for recurrent Sertoli Leydig cell tumor is unknown. Initial plans of management of this rare neoplasm, follow-up, and current concepts of treatment of recurrences will be discussed.

Sertoli-Leydig cell tumor of the ovary with teratomatous differentiation: clinicopathologic considerations.

A patient with recurrent Sertoli-Leydig cell tumor is described. The light and ultrastructural findings are illustrated. The tumor recurred first as a poorly differentiated tumor with rhabdomyoblastic differentiation. Following chemotherapy the next recurrence exhibited well differentiated Sertoli-Leydig cell elements. These findings may reflect the capability of this tumor type to undergo chemotherapeutic transformation similar to the transformation which has been described in germ cell tumors of the ovary and testis. This observation may be of importance in the clinical management of patients with poorly differentiated Sertoli-Leydig cell tumors.