1Ümraniye Training and Research Hospital, Pediatric Endocrinology, 34766 Istanbul, Turkey
2Ümraniye Training and Research Hospital, Radiology, Istanbul, Turkey
3Ümraniye Training and Research Hospital, Pediatric Surgery, Istanbul, Turkey
4Ümraniye Training and Research Hospital, Pathology, Istanbul, Turkey
5Göztepe Training and Research Hospital, Pediatric Oncology, Istanbul, Turkey
A 4-year-old boy was referred to pediatric endocrinology because of bilateral breast enlargement
Q What is importance of age of presentation of gynecomastia ?
- During neonatal period, puberty and in elderly, gynecomastia is physiological.
- Gynecomastia in prepubertal children and in young- middle age adults is unusual and pathlogical causes of gynecomastia must be sought in these patients.
Q What are the causes of Prepubertal gynecomastia ?
- Drug induced
- Aromatase excess syndrome
- Chronic liver disease
- Chronic renal disease
- Testicular tumor
- Adrenal tumors
There was no history of a chronic disease, medication, or a familial disorder.
Q Name some common drugs that lead to gynecomastia ?
- Spironolactone – used in hypertension and CCF
- Finesteratide – 5 alpha reductase inhibitor used in BPH
- Cimitidine- H2 receptor antagonist used in peptic ulcer management
- Growth hormone
- Anti-androgen – like flutamide- used in prostate cancer.
Height was 114 cm (+1.2 SDS), weight was 20 kg (+0.7 SDS), and physical examination revealed bilateral gynecomastia.
Breast development appeared as Tanner Stage-2 (Figure 1)
Q What is Tanner stage 2 of breast ?
- Presence of breast bud is Tanner stage 2
- Areola starts to develop with small amount of breast tissue.
axillary and pubic hair were absent, stretched penile length was 6 × 1.5 cm, and right testis was 2 mL and left testis was 5 mL
Q What is unusual here ?
Asymmetrical testicular enlargement.
Q What is the mean streached penile length at this age ?
The mean SPL would be around 5.6 cm. Here it is around 6 cm , which is normal.
Q How will you evaluate this case further on from here ?
- This is clearly a case of prepubertal gynecomastia which is unusual.
- I would consider endocrine evaluation as well as scrotal ultrasound to evaluate the asymmetrical testicular enlargement.
- For the endocrine evaluation, I would order an LH, Testosterone, E2, and HCG levels.
- Additional I would ask for a bone age of the child.
Hormone levels were in normal ranges (Table 1); tumor markers were negative while scrotal ultrasonography (USG) exhibited a 8 × 12 mm solid lesion with cystic component in the left testis.
Q What is your interpretation of the evaluation ?
- Bone age is advanced.
- There is a testicular mass which needs assessment.
- LH and Testosterone are in Normal prepubertal range.
- Other hormonal investigations are normal.
Q Which testicular tumors are associated with gynecomastia ?
- HCG producing germ cell tumors of testis
- Leydig cell tumor
- Large calcifying Sertoli cell tumors typically seen in Carney’s complex or Peutz Jaghers syndrome.
Q What are DD of testicular mass ?
- Testicular adrenal rest tissue (TART)
- Testicular tumor
Q Why is testicular biopsy not routinely performed for such lesion ?
This is because there is risk of seeding of the tissue and spreading of the malignant tissue
Q Which is the first and most important step in evaluation of a male with testicular mass ?
Q What are the USG apperance of seminoma and non seminoma ?
- Seminomas- well defined hypoechoic areas without cysts
- Non seminomas- indistinct margins, calcification, cysts and inhomogenous
Q What is done is incidental testicular lesion is found in scrotal ultrasound ?
- Go for tumor marker
- If negative- ultrasound follow up is adequate
Q Which are the tumor markers for testicular Germ cell Tumors ?
- Beta HCG
Q What is the relation between type of cancer and the tumor markers ?
- Non Seminomas- beta HCG and/or AFP is elevated in 80% of cases
- Seminomas- beta HCG is elevated in 20% cases, AFP is not elevated
Q Are tumor makers alone sensitive to diagnose GCT ?
- They are not sensitive enough to make a diagnosis without histological confirmation
Q Which is the gold standard for diagnosis of testicular GCT ?
- Radical inguinal orchiectomy is the gold standard for diagnosis of testicular GCT
- It gives histopathological confirmation
- Neither ultrasound nor tumor markers can replace it
Q What is the next step for this child ?
The child has tumor marker for GCT which are negative.
- However, since the child has gynecomastia and advanced bone age with this testicular mass, evaluation is required.
- I would consider doing an orchidectomy of the involved testis.
The committee on tumoral diseases agreed on the decision to perform a testis-sparing surgery in the light of examination of frozen sections. However the large and cystic mass left no adequate testis tissue to conserve, so a left orchiectomy was performed.
Abdomen and thorax Computed Tomography (CT) imaging were normal. Histopathological investigation revealed a sertoli cell tumor which had positive staining with inhibin, vimentin, and calretinin. Gynecomastia regressed at the end of three months following the operation.
Q Sertoli cell tumors are associated with which conditions ?
- Carney’s complex
- Peutz Jeghers syndrome
Q What is the characteristic of these tumor in Carney’s complex ?
- They are large cell calcifying Sertoli cell tumors
- They generally appear in the 2nd decade
- They are generally non hormonal producing
Q What is the feature of the tumor in Petz Jeghers ?
They have high aromatase activity and hence they often produce gynecomastia
Q What about Sertoli cell tumors which are not a part of the above disorders, are they hormonally active ?
No, They are not
Q Which is the most common testicular tumor in infants ?
- Juvenile granulosa cell tumor is the most common testicular tumor in infants
- It occurs in first few months of life
- They generally have good prognosis
- They rarely present with ambigious genitalia
Q What about adult granulosa cell tumors ?
- They are more likely to be hormonally active
- They present in middle age with gynecomastia and feminizing features
Q Which important immunohistochemical is common in the various sex cord tumors ?
Q Why are sertoli cell tumors more likely to produce estrogen compared to Leydig cell tumors ?
- Sertoli cell tumors have aromtase enzyme expressed in them.
- Hence they are more likely to produce estrogen.
- They mainly produce Estrone from androstenadione in prepubertal boys.
- Sertoli cell tumors have high aromatase activity and hence can present with gynecomastia. However, most sertoli cell tumors occur in context of PJS or Carney’s complex and are often bilateral. Unilateral Sertoli cell tumor presenting with gynecomastia in prepubertal child without evidence of any syndrome is rare.
- Drugs are the most common cause of prepubertal gynecomastia.