Sertoli Cell Tumor of the Testis in Association with Peutz-Jeghers Syndrome Sometimes Requires a High Index of Suspicion

Patients with PJS may develop testicular neoplasms in a variable percentage of cases⁴. These belong to stromal tumors derived from Sertoli cells⁵. The large-cell calcifying Sertoli cell tumor was first described by Proppe and Scully⁶. In most cases it appears in phenotypically normal patients as a single, firm nodule but up to one third of cases⁵ are associated with genetic or endocrine syndromes as Carney Syndrome or PJS. In such cases neoplasms are commonly bilateral, multifocal, smaller and they appear earlier^5,7, as in our patient. The testicular lesion specifically associated with PJS is called Intratubular large cell hyalinizing Sertoli Cell (LCHSC) neoplasia⁷ and is similar to the sex cord tumor with annular tubules of the ovary that appears in women with PJS⁸.

Histologically, the lesion shows a patchy distribution of enlarged tubules, which exceed several times the diameter of unaffected tubules. Sertoli tumor cells are large with vacuolated and eosinophilic cytoplasm. Tubules can be replaced by basement membrane deposits, giving a hyalinized appearance⁷. Another feature is the presence of calcifications, not always present in cases of PJS^7,9, but seen in our patient. In some cases Intratubular Sertoli Cell Proliferations (ISCPs) have been described. They emerge from seminiferous tubules and gradually replace the cell population. There is controversy about whether ISCPs are non-neoplasic proliferative lesions with malignant potential or represent an intraepithelial stage of tumor development. Although in some patients ISCPs are the only pathological finding, they may appear nearby to large-cell calcifying Sertoli cell tumor¹⁰. Some authors argue that they are the testicular neoplasm specifically associated to PJS^7,11.

Extratubular growth implies potentially malignant nature irrespective of local characteristics⁴. Malignancy is found in approximately 17% of patients with large-cell calcifying Sertoli cell tumor⁹, ussually in older patients with unilateral and unifocal mass^8,9. In patients with PJS reviewing of published cases finds that local infiltration is very uncommon, so the process often remains confined to the tubules for long periods of time². Anyway, it should be note that the follow-up period of these patients is limited since first cases date from the 80´s and progression to invasive tumor cannot be rule out¹². Venara et al¹⁰ described a patient with a follow up of more than 30 years with no evidence of progression. Although histological malignancy index have been described (high mitotic rate, nuclear atypia, necrosis and vascular or lymphatic invasion)^8,9, the question of which damage may progress is still unknown⁷.

Tumor cells have increase activity of aromatase enzyme¹⁰, which normally is produced by Leydig cells⁹. This determine a higher conversion of testosterone to estradiol. As a result, patients with LCHSC typically have clinical signs of estrogenic activity that lead to the suspicion of the tumor, such as acceleration of growth with avanced bone age⁹ and gynecomastia¹⁰. However, cases of incomplete penetrance have been already described 15 and peripubertal gynecomastia not necessarily related to the tumor was appreciated in our patient.

The course of evolution of this condition justifies its conservative management monitoring by ultrasounds. Surgery could be indicated in selected cases of unusual invasive tumors, pain or mass effect. Hormonal manifestations could be treated with aromatasa inhibitors¹³, like testolactone and anastrozol. These drugs can be effective in controlling the clinical features of the disease, like breast development, growth velocity and bone maduration¹⁶ but evidence is limited and further studies are required⁹. In our patient no hormonal abnormalities were found and bone age and growth was normal so it was decided to keep monitoring. Later ultrasound controls show no change compared to previous.

The case reported here represents an unusual presentation because it appears in an asymptomatic boy with almost no estrogenic manifestations unless mild gynecomastia. The lesion was diagnosed during a routine check, which should make us question the kind of monitoring strategies in these patients with increased risk of cancer. In case of testicular neoplasms surveillance strategies are based on expert opinion only. It is recommended to perform annual physical examination and ultrasound in case of detection abnormalities or signs of precocious puberty¹. Anyway, it should be noted that average age of presentation of these tumors is earlier than in others cancers associated to PJS^1,4,8. As in our case, diffuse and bilateral testicular involvement can overlook the presence of changes on physical examination¹³ and the development of secondary hormonal disturbances may not be present at an early stage. Hyperestrogenism cannot be detected in laboratory tests because the hormone excess is limited to testicular aromatase¹⁴, which may explain the findings in our patient.

Conclusions

Our case highlights the need to establish a high index of suspicion of testicular tumors in patients with PJS. Although LCHSC usually remains confined locally, can lead to endocrine disorders with impact on growth and pubertal development in children. It is necessary to establish preventive diagnostic strategies from an early age in these patients.

Acknowledgments

The authors thank Dr. M. Nistal, Department of Pathology, La Paz University Hospital, for providing histopathological assistance.

References

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