Pediatric Testicular Tumors. Mark A. Williams, MD Joe Welser, MD February 12, 2014
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1 Pediatric Testicular Tumors Mark A. Williams, MD Joe Welser, MD February 12, 2014
2 Testicular Tumors 1% to 2% of all Pediatric Solid Tumors Annual Incidence of 1 in 100,000 Majority occur in children < 2 years of age Teratoma now thought to be most common type Benign Tumors Account for 38% of cases Metastasis (Occurs in < 15% of tumors) 28% to Lymph Nodes 40% Hematogenous 20% Both
3 Classification Germ Cell Benign Teratoma Epidermoid Cyst Malignant Yolk Sac Gonadal Stromal Para-Testicular Leydig Cell Juvenile Granulosa Cell Lipoma Leiomyoma Sertoli Cell Rhabdomyosarcoma
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5 Tumor Proportion By Type Yolk Sac Teratoma Epidermoid Cyst Leydig Cell Sertoli Cell Granulosa Cell Gonadoblastoma Other
6 Tumor Proportion By Age
7 Link to Cryptorchidism Incidence of testicular cancer in general population is approximately 5.4 per 100,000 Wood and Elder (2009): Relative Risk of Malignant Transformation 2.75 to 8 overall (< 0.5%) 2 to 3 in boys undergoing prepubertal orchiopexy Boys undergoing postpubertal orchiopexy are 2 to 6 times more likely to develop testicular cancer 74% of malignancies in persistent cryptorchid testes, are seminoma 63% of malignancies in post-orchiopexy patients, are nonseminoma No increased risk for tumors in the contralateral normally descended testis
8 Link to Cryptorchidism (ctd) Cortes, et al (2004): Incidence of Pediatric Testicular Tumors in Patients with Cryptorchidism 3.8% of children with abdominal undescended testes, abnormal external genitalia, or abnormal karyotype In patients without these characteristics, no cases of testicular neoplasia Found most often in bilateral cryptorchidism Petterson, et al (2007): Relative risk increases with age at orchiopexy Relative risk increases the more cephalad the undescended testis Other studies show presence of cancer in contralateral testis in 20% of cases
9 Chromosomal Abnormalities Benign Teratoma: No abnormality Yolk-Sac Tumors: del(1p36) in 80% - 100% of cases Intratubular Germ Cell Neoplasia: i(12p) Post-Pubertal Germ-Cell Tumors Loss of chromosomes 11, 13, or 18 Gain of chromosomes 7, 8, or X Patients with Disorders of Sex Development (DSD) have increased incidence Hypovirilization and gonadal dysgenesis are at higher risk Presence of Y chromosome in gonadal dysgenesis increases risk to 10% by age of 20 Intratubular germ cell neoplasia has been noted in 6% of children with DSD
10 Diagnosis Most common Presentation: Painless testicular mass 10% with history of hernia or hydrocele 15% - 50% have hydrocele on physical exam May also present with acute abdominal pain Must rule out epididymitis, hydrocele, hernia, and torsion (neonate) Testicular Ultrasound (with doppler): Cannot reliably distinguish benign and malignant tumors Anechoic cystic lesions suggest benign lesion Sharp borders and low flow suggest benign Useful to evaluate whether there is enough useful testicle to salvage
11 Tumor Markers a-fetoprotein elevated in > 90% of yolk-sac tumors All a-fetoprotein producing tumors have yolk-sac elements T 1/2 of 5 days Elevated for 6-9 months postpartum Also elevated in hepatoblastoma b-hcg not useful in prepubertal patients Embryonal carcinoma and choriocarcinoma are rare Produced by some mixed teratomas
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14 Yolk Sac Tumor AKA endodermal sinus tumor, embryonal adenocarcinoma, infantile adenocarcinoma of the testis, orchidoblastoma, or Telium tumor Most common malignant tumor in infants and young boys 3% of cases have a positive history of trauma Staging a-fetoprotein CT of chest and abdomen
15 Yolk Sac Tumor - Pathology Gross Pathology Microscopic Appearance
16 Yolk Sac Tumor Pathology (ctd) Schiller-Duvall Bodies Hyaline-like Globules
17 Children s Oncology Group Staging System for Yolk Sac Tumors I II III IV Limited to testis Completely resected by high inguinal orchiectomy Tumor markers negative Unknown tumor markers at diagnosis -> Need negative ipsilateral retroperitoneal lymph node biopsy if > 2cm on CT Microscopic residual disease Tumor markers remain elevated Tumor rupture or scrotal biopsy prior to complete orchiectomy Retroperitoneal lymph node involvement (> 4 cm on CT) RPLN < 4 cm, but > 2 cm need biopsy Distant Metastasis
18 Yolk Sac Tumor - Treatment More than 90% present with Stage I disease Initial treatment: Radical inguinal orchiectomy (curative in most patients) Confirmed Stage I: Surveillance (36 months) Physical Exam + AFP CXR + CT/MRI of retroperitoneum Q1Month x 3, Q3Month x 1, Q6Month x 5 Stage II and Above: Platinum-Based Chemotherapy (BEP) Side effects: Ototoxicity, Nephrotoxicity
19 Yolk Sac Tumor Treatment (ctd) Routine RPLND not indicated Evidence of Residual or Recurrent disease Normal or unknown AFP at diagnosis Persistent retroperitoneal mass after chemotherapy Persistent elevation of AFP with negative imaging after chemotherapy Survival (6-year EFS) Stage II: ~100% Stage III: ~100% for age < 15 vs 83.3% Stage IV: 94.4% for age < 15 vs 84% Histology in patients < 15 was pure yolk-sac tumor (83%) vs mixed germ-cell tumor in patients > 15
20 Teratoma Most common pediatric testis tumor Comprised of elements of more than one germ cell layer: endoderm, ectoderm, mesoderm Two types, both almost always benign Mature Teratoma Immature Teratoma: Immature tissue usually neuroepithelium Occasionally malignant Usually has yolk-sac tumor component
21 Teratoma Gross Pathology Mature Teratoma Immature Teratoma
22 Teratoma Microscopic Appearance Mature Teratoma Immature Teratoma
23 Teratoma (ctd) Diagnosis Ultrasound of testis reveals a heterogeneous lesion with internal echoes (calcification) AFP not elevated for the patient s age Treatment Testis-sparing procedures (enucleation) Should be done through inguinal incision Teratomas generally shell out easily due to pseudocapsule around the lesion
24 Epidermoid Cyst Monodermal Teratoma Differentiated squamous-lined cysts Filled with keratinous debris AFP levels normal Suggested by characteristic appearance on ultrasound: Concentric rings of alternating hypo and hyperechoic layers ( onion-skin appearance) Benign: May be managed by eneucleation
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26 Epidermoid Cyst - Pathology Gross Pathology Microscopic Appearance
27 Leydig Cell Tumor Most common stromal tumors of testis in children Peak incidence at 4 to 5 years old Arise from a common mesenchymal stem cell that can differentiate into Leydig cells, Sertoli Cells, or granulosa cells Secrete testosterone: Cause 10% of precocious puberty in boys < 9 years old Classic triad Testis mass Precocious puberty Elevated serum testosterone and urinary 17-ketosteroids
28 Leydig Cell Tumor (ctd) Differential Diagnosis Pituitary Lesions Leydig Cell Hyperplasia Large Cell Sertoli Cell Tumors Hyperplastic Testicular Nodules in Boys with CAH Treatment Resection (testis-sparing) is curative Hormonal effects not reversible
29 Leydig Cell Tumor - Pathology Gross Pathology Microscopic Appearance
30 Leydig Cell Tumor Pathology (ctd) Reinke s Crystals Germinal Epithelium Stimulated in Prepubertal Boy
31 Sertoli Cell Tumors Presents at earlier age than Leydig Cell Tumors 10% Hormonally Active: Gynecomastia most common effect 1/3 Associated with Genetic Syndromes Peutz-Jehgers syndrome Carney Complex Treatment Observation in Infants (Metastasis Rare) Metastasis Can Occur in Older Boys (10% overall rate) Orchiectomy (Eneucleation in pre-pubertal boys) Must Exclude Retroperitoneal Spread
32 Sertoli Cell Tumor - Pathology Gross Pathology Microscopic Appearance
33 Juvenile Granulosa Cell Tumor Most common testicular tumor of neonates Presents most often in the first 6 months of life (often detected at birth) May occur in children with ambiguous genitalia, intersex disorders, and sex-chromosome mosaicism Not associated with precocity Benign without recurrence Eneucleation (testis-sparing) is curative
34 Juvenile Granulosa Cell Tumor Gross Pathology Microscopic Appearance
35 Gonadoblastoma Found in association with disorders of sex differentiation Occur in abnormal gonads 22% streak, 18% dysgenetic, 60% indeterminate Originate in Surviving OCT-3/4 Positive Germ Cells in Areas of Undifferentiated Gonadal Tissue Combination of Germ-Cell Tumor and Gonadal Stromal Tumor Associated with the presence of Y chromosome 80% occur in phenotypic females with 46 XY Mixed gonadal dysgenesis 25% risk of tumor formation Incidence increases with age
36 Gonadoblastoma (ctd) Occur bilaterally in 10% 33% of cases Benign in childhood As germ-cell elements outgrow stroma 10% - 60% will progress to dysgerminoma (seminoma) after puberty Treatment: Prepubertal gonadectomies in atrisk patients All streak gonads should be removed All undescended testes should be removed
37 Gonadoblastoma - Pathology Gross Pathology Microscopic Appearance
38 Intratubular Germ Cell Neoplasia Carcinoma In Situ Found in 80% of testes with malignant germcell tumors (8% contralateral) Rarely in prepubertal germ-cell tumors Found in 2% - 8% of testes with cryptorchidism 90% of adults will develop a clinical germ-cell tumor within 7 years Treatment: Orchiectomy or Radiation
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44 Testicular Microlithiasis Calcium testicular stones Found (usually incidentally) in 0.5% - 1% of all men, being discovered more frequently in children 80% Bilateral No confirmed relationship with testicular cancer But, found in 50% of testes removed for tumors Treatment: Testicular Self-Examinations
45 Testicular Microlithiasis (ctd) Appearance on Ultrasound ITGCN and Microlithiasis
46 Paratesticular Rhabdomyosarcoma 5% of testicular tumors Most often arises in distal portion of spermatic cord and may invade testis of surrounding tissues 60% occur in the first 2 decades of life Bimodal age distribution 3-4 months 16 years Arises from mesenchymal tissue 90% embryonal variant (better prognosis) 30% - 50% have metastasis (usually lymph node) at diagnosis
47 Paratesticular Rhabdomyosarcoma
48 Paratesticular Rhabdomyosarcoma - Pathology Gross Pathology Microscopic Appearance
49 Paratesticular Rhabdomyosarcoma Pathology (ctd) Rhabdomyoblasts More Rhabdomyoblasts
50 Paratesticular Rhabdomyosarcoma Grouping and Staging
51 Paratesticular Rhabdomyosarcoma - Prognosis
52 Paratesticular Rhabdomyosarcoma Diagnosis and Management Usually presents as unilateral painless scrotal swelling or mass that is distinct from testis Ultrasound can be used to confirm solid nature of lesion 60% to 80% are stage 1 at presentation Initial Treatment: Radical Inguinal Orchiectomy CT scan for staging Enlarged nodes have 65% - 94% chance of positive pathology 14% false negative rate Chemotherapy alone (Vincristine and Actinomycin D) produced 5-year survival of 99.1% in low-risk patients (favorable histology, T1N0M0, Clinical Group I)
53 Paratesticular Rhabdomyosarcoma - RPLND Full RPLND morbid with up to 25% rate of serious complication Children > 10 years of age should have ipsilateral RPLND for staging before chemotherapy Relapse-free survival lower than in younger boys Patients with positive lymph nodes require intensified chemotherapy as well as nodal irradiation VAC = Vincristine, Actinomycin D, Cyclophosphamide Overall Survival > 90%
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