UTP5 - Testiculo e Pénis - Cancro (1) Flashcards
Testicular Cancer?
◆ Testicular cancer accounts for only about 1% of all human neoplasms
◆ Testicular cancer although rare is the most common solid malignancy in men in the 15-35 years age group and accounts for approximately 23% of all cancers in this group
Epidemiology?
◆ Median age at diagnosis: 34 years (50% between 20 and 34 years)
◆ 3 incidence peaks: 2-4 years; 20-40 years; above 50 years
◆ > 50 years: Lymphoma more common
◆ Geography
– Highest incidence: Denmark, Norway, and Switzerland
– Lowest: Eastern Europe and Asia
◆ Race
– More common: Young white men
– Less: African americans
Epidemiology (2)? IMPORTANT
◆ 90-95% of testicular tumors are malignant germ cell tumors
◆ Germ cell tumors
– Seminomas (45%)
– Non Seminomas (45%)
. Mixed (35%)
. Pure (10%)
◆ Non-Germ cell tumors (5-10%)
– Sex cord / gonadal stromal tumors
– Lymphoid and hematopoietic tumors
◆ PS: Tumor testicular é o único com metastização curativa
Embriology?
◆ Insulin-like hormone 3 dependent
- 3rd month - iliac fossa
- 4th - 6th month - deep inguinal ring
◆ Androgen dependent
- 7th month - inguinal canal
- 8th month - superficial inguinal ring
- 9th month - scrotum
Testicular cancer - Types?
◆ Seminoma: 10-15% with syncytiotrophoblast cells (pode ter BHCG aumentada)
◆ Embryonal carcinoma and Yolk sac tumor = Virtually pluripotent
◆ Germ cell tumors Teratoma
Histology - frequency?
◆ Spermatocytic tumor with sarcoma - mais comum na idade adulta >60 anos
Genomics?
◆ Adult testicular and extragonadal germ cell tumors
– Ubiquitous gain of isochromosome 12p
– Low rates of somatic mutations and genetic mutations (i.e. KIT, KRAS)
– Polygenic variation in the absence of a major high-penetrance susceptibility gene
Epigenetic mechanisms?
◆ Chromatin remodeling
◆ MicroRNA regulation
◆ DNA promoter methylation
– Seminomas - extensively hypomethylated
– Nonseminomas - higher DNA methylation (similar to other solid tumors)
Genomics and therapy?
◆ Highly sensitive to DNA damaging agents (except teratomas)
◆ Platinum-resistant disease
– High rates of alterations within the TP53-MDM2 axis
◆ Potential targets
– TP53-MDM2, PI3 Kinase, MAPK signaling pathway, MSI/MMR
Predisposing factors? IMPORTANT
◆ Cryptorchidism / Delayed orchidopexy (> 10 years) / Gonadal Dysgenesis
◆ Klinefelter syndrome
◆ Positive family history
◆ Positive personal history
◆ Intratubular germ cell neoplasia
Fator que afeta mas não associação comprovada?
- Trauma
- Viral infection
- Hormonal factors
- Environmental estrogens (ex.: diethylstilbestrol)
- Marijuana?
Lymphatic Drainage?
◆ On the right – drena para os dois lados
◆ On the left – drena apenas para o lado esquerdo
Lymphatic Drainage (2)?
◆ Common iliac, external iliac, and inguinal lymph metastatic nodal disease
– Usually secondary to large-volume disease with retrograde spread
◆ Metastasis to the pelvic and inguinal lymph nodes (tipicamente em pessoas que foram intervencionadas cirurgicamente na infancia nessa zona)
– If herniorrhaphy, vasectomy, or other trans-scrotal
◆ Thoracic duct
– Main route to the posterior mediastinum, supraclavicular fossae, and axillary nodes
◆ Contralateral spread
– Mainly right-sided tumors
◆ Bilateral lymph node involvement
– 15-20 %
Diagnosis? IMPORTANT
◆ Local examination
– Enlarged testis (except choriocarcinoma)
– Nodular, firm to hard, testis
– Loss of testicular sensation
– Flat and difficult-to-feel epididymis
– Secondary hydrocele
– Acute pain
◆ General examination for metastasis
– Abdominal or lumbar pain (lymphatic spread)
– Dyspnoea, hemoptysis, and chest pain with lung mets
– Jaundice with liver mets
– Hydronephrosis by para-aortic lymph nodes enlargement
– Peripheral edema by IVC obstruction
– Trosier’s sign
Staging and Imaging?
◆ Ultrasound - Calcifications !!!
◆ CT
– 70-85 % accuracy (3 mm, with path correlation)
– Micrometastases !!!
◆ MRI
– Vascular involvement
– Cerebral involvement
– Increasing role in surveillance
◆ PET
– Post-chemotherapy seminoma residual mass
– Teratoma versus fibrosis !!!
