Benign and Malignant Genital Disorders Flashcards
1. Describe the anatomy, presenting features, and management options for the commonly encountered benign scrotal masses. (MKS 1b, 1d, 1e) 2. Describe the anatomic abnormalities predisposing to testicular torsion, the common presenting signs/symptoms, useful diagnostic tests and the rationale underlying prompt surgical management. (MKS 1b, 1d, 1e) Describe the standard precepts of diagnosis, staging, and management of testicular, penile, & urethral tumors. (MKS 1d, 1e)
1
Q
Differentiate between the following: hydrocele, spermatocele, epididymal cyst, varicocele, scrotal hernia, and epididymitis.
A
- A hydrocele is an abnormal amount of fluid contained between the parietal and visceral layers of the tunica vaginalis
- A spermatocele is a cystic mass emanating from the rete testis, which contains seminal fluid (and spermatozoa).
- An epididymal cyst contains a clear fluid (without spermatozoa), and projects from the epididymal surface. These masses exhibit (+) transillumination
- Scrotal ultrasonography can provide further anatomic clarification and help define the scrotal structures, if the latter are difficult to palpate
- A varicocele consists of a dilated network of incompetent veins constituting the pampiniform plexus (varicocele).
- This condition may be associated with infertility due to an elevation in intrascrotal temperature, which interferes with normal spermatogenesis
- They are most commonly encountered on the L side & can be graded, as follows:
- Grade 1—palpable with Valsalva
- Grade 2—palpable w/o Valsalva
- Grade 3—visible
- A scrotal hernia represents a patent processus vaginalis (i.e., inguinal hernia)
- Epididymitis nay be associated with pain, swelling, and constitutional symptoms (elevated temperature, chills) and is often associated with a urinary tract infection
2
Q
What is the presentation and diagnosis of testicular torsion? How is it managed?
A
- Testicular torsion is generally a disease of post-pubertal males but over 1/3 of these cases occur in men ≥21 years old
- Two forms of testicular torsion have been recognized:
- Extravaginal torsion results when the testis and the cord twist because of non-fixation of the testis, cord, and processus vaginalis, as in newborns and patients with undescended testes
- Intravaginal torsion (the most common type) takes place within the tunica vaginalis and results from an abnormally high investment of the tunica on the spermatic cord within the scrotum (ie bell-clapper deformity)
- The diagnosis is often apparent after performing a thorough history (abrupt onset, absence of infection-like symptoms, previous self-limiting episodes) and physical examination (high-riding testis, hypermobile testis, “bell clapper” deformity, diffuse/painful scrotal swelling)
- A scrotal ultrasound study (with color Doppler) can be helpful in equivocal cases
- Orchiopexy involves anchoring both testes to their respective dartos fascia because the anatomic defect predisposing to torsion is bilateral in >50% of cases
- Obviously, if the involved testis is no longer viable—it should be removed
3
Q
What is the epidemiology of testicular cancer?
A
- Uncommon malignancy, which accounts for about 1.5% of all solid tumors in men
- Approximately 8,980 cases of malignancy are anticipated annually (~ 5.4 cases per 100,000 men—U.S. Caucasians)
- For reasons that are unclear, the incidence of this cancer has steadily increased since the turn of the century (in the Caucasian population)
- Testicular cancer is most common between the ages of 20 and 40 years
- The disease is rare in African-Americans (~ 0.9 cases per 100,000 U.S. Blacks)
- Although there are no significant differences in tumor type and clinical stage at presentation, African-American men with testis cancer have a significantly decreased 5-year disease-specific survival when compared with Caucasian men (71% vs. 88%)
- With respect to geographic predilection, Scandinavia has the highest incidence of testicular cancer (9.3 cases per 100,000 men), while the Far East has the lowest
- In men over the age of 50, the most common testis tumor is a lymphoma – while the most common germ cell tumor is a spermatocytic seminoma
- Finally, cancers that may metastasize to the testes include: prostate, lung, melanoma, and kidney
4
Q
What is the molecular pathogenesis of testicular cancer?
A
- Most of these tumors originate from pluripotential germ cells and originate in the testis (90%)
- The isochromosome of the short arm of chromosome 12 [i (12p)] is a unique chromosomal marker of germ cell tumors of all histologic types (including carcinoma-in-situ) and can be identified in over 80% of such neoplasms
- Of importance, the genes encoding cyclin D2 (increases cell proliferation) and LDH (tumor marker, especially in seminomas) reside on 12p, which accounts for their amplified expression in these tumors
- Sites of extragonadal involvement include the retroperitoneum, mediastinum, and the pineal gland
5
Q
What are the risk factors of testicular cancer?
A
- A number of risk factors have been identified
- The strongest is a prior history of testis cancer
- About 1-4% of patients will develop a tumor in the contralateral testis over time (70%-80& metachronous,; 20%-30% synchronous; median time between tumors is ~ 5 years; seminoma most common histology)
- Patients with cryptorchidism (and delayed orchidopexy > 10 years of age) have a 3-8X increased risk of developing testis cancer
- Patients with Klinefelter’s syndrome are at risk for germ-cell tumors, particularly those arising in the mediastinum
- Human immunodeficiency virus infection is also associated with significantly increased risk of testis cancer, in addition to non-Hodgkin’s lymphoma of the B-cell type, Kaposi sarcoma, and SCCa of the anus
- The association between testicular microlithiasis and germ cell neoplasia is poorly defined
- However, if microlithiasis is bilateral and found in a subfertile man with testicular atrophy or is present in the contralateral testis of a patient with germ cell neoplasia—then a higher likelihood of in situ disease exists and regular self-examination is advised
- There is also an association of Down’s syndrome and testis cancer
- Despite previous reports, in utero exposure to diethylstilbestrol is not a strong risk factor
- Other acknowledged risk factors include: family history; gonadal dysgenesis; androgen insensitivity syndrome; and marijuana consumption.
6
Q
What are the presenting symptoms of testicular cancer?
A
- The patient may present with signs/symptoms referable to the local process (scrotal mass +/- pain, hydrocele) or those related to disseminated disease
- Epididymitis is mistakenly diagnosed in 20%-30% of cases. Back and abdominal pain may result from massive retroperitoneal lymphadenopathy
- Mediastinal adenopathy may be associated with chest pain or cough
- Patients with massive pulmonary metastasis may present with dyspnea, cough or hemoptysis
- Symptomatic CNS metastases are most often seen in patients with hematogenous dissemination of choriocarcinoma or a pure yolk sac tumor
- Painful osseus metastasis may also occur (most often with advanced-stage seminoma)
- Abdominal distension and upper abdominal pain may be seen patients with hepatic metastasis
- Patients with primary mediastinal germ-cell tumors may present with acute megakaryocytic leukemia
7
Q
How are testicular tumors diagnosed?
A
- Many primary tumors are detected as a result of testicular self-examination
- Any solid testicular mass (particularly one associated with induration and pain) is assumed to be neoplastic until proven otherwise
- Indeed, about 95% of patients with a mass within the testis have malignancy
- Scrotal ultrasonography can be used to confirm the presence of a solid intratesticular mass
- Most of the latter are hypoechoic, but hyperechogenicity can be seen with teratomas—which may contain echo-dense tissue sub-types (i.e., bone, cartilage)
- Ultrasound scanning of the “normal” contralateral testis may reveal an unsuspected malignancy in 1-2% of cases
8
Q
What are some tumor markers for testicular cancers?
A
- Obviously, a thorough history and physical examination should be performed
- With respect to the latter, the presence of bilateral gynecomastia may reflect the presence of high circulating levels of human chorionic gonadotropin (t ½ = 24-36 hours)
- The latter tumor marker is a product of syncytiotrophoblastic activity and can be seen in both seminomas and non-seminomatous germ cell tumors
- Assays should also be obtained for alpha-fetoprotein (t ½ = 5-7 days), whose elevation is indicative of yolk sac elements within the tumor (and NEVER seen in a pure seminoma)
- All testis tumors (especially, but not exclusively seminomas) can be associated with LDH elevations
9
Q
What is the initial management of testicular cancer?
A
- Virtually all adult patients will require an inguinal (radical) orchiectomy as the first step in treatment
- Testis-sparing surgery is more commonly performed in infants
- Radical orchiectomy permits the removal of the spermatic cord to the level of the internal ring, which facilitates the elimination of “in transit” tumor cells within the lymphatic/vascular channels of the cord
- In addition, the inguinal approach avoids contaminating the scrotal lymphatics (inguinal lymph nodes), which are generally not involved in this disease process
- The testes drain to the upper retroperitoneal lymph nodes. Right-sided tumors preferentially target the inter-aortocaval nodes
- Left-sided tumors selectively colonize the left perihilar/aortic nodal basin. Right to Left “crossover” is common
10
Q
What is the histopathology of testicular cancers?
A
- Carcinoma in situ (PLAP–placental alkaline phosphatase +) is thought to be precursor of all invasive germ-cell tumors (except spermatocytic seminoma, pediatric teratoma, & pediatric yolk sac tumor)
- Testis cancers are classified into two broad categories: seminoma and nonseminomatous germ-cell tumors
- Seminoma is the most common histology and tends to occur in older patients
- β-hCG may be elevated in 10-15%% of seminomas. AFP is never expressed by pure seminomas
- Nonseminomatous tumors may be associated with the elevation of β-hCG and/or AFP
- Seminomas do not express markers of somatic differentiation such as keratins, but do express PLAP and CD117 (the kit receptor)
- EC, choriocarcinoma, and yolk sac carcinoma do express low-molecular weight cytokeratins and the CD30 antigen
11
Q
How are testicular cancers staged?
A
- Testis cancers generally metastasize in a relatively predictable fashion (from the testicle to the retroperitoneal lymph nodes and later hematogenously to the lungs or other sites)
- The standard staging work-up includes a chest X-ray and CAT scans of the abdomen and pelvis
- CAT imaging of the lungs is performed if the chest X-ray is abnormal
- An MRI is obtained in cases of suspected vascular involvement (IVC)
- PET scans are usually obtained to further evaluate post-chemotherapy residual masses in patients with advanced-stage seminoma
- The currently TNM staging classification is depicted in Appendix A
12
Q
How are seminomas managed?
A
- Following inguinal orchiectomy, patients with clinical stage 1 seminoma may be observed with the realization that 13-19% of these patients will subsequently relapse
- This is the most common management option that is currently practiced in this country
- The most favorable criteria for surveillance include: pure seminoma histology; normal tumor markers; clinical stage 1; tumor size < 4 cm; no rete testis invasion; no lymphatic/vascular invasion; and a compliant patient
- The median time to relapse is 12-18 months, but late relapses beyond 5 years have been reported
- In Europe, such patients are increasingly treated with 1-2 cycles of single-agent carboplatin (0.8% retroperitoneal recurrence; contralateral testis cancer in 2.2% of patients)
- In the USA, low-stage (I, IIa, IIb) seminomas may also be treated with low dose (2500-3000cGy) radiation to the retroperitoneal lymph nodes
- Contraindications to radiation therapy include
- (1) previous abdominal radiation
- (2) history of inflammatory bowel disease
- (3) presence of a horseshoe kidney, renal transplant, or pelvic kidney
- (4) history of previous bilateral retroperitoneal lymph node dissection
- Advanced stage (IIc, III) seminoma is treated with chemotherapy, which generally involves the use of cisplatin, ectoposide (VP-16) and bleomycin (i.e. PEB regimen)
13
Q
What is the management of non-seminomatous germ cell tumors?
A
- Patients with nonseminomatous tumors are treated somewhat differently
- For those patients with clinical stage I disease, 20-55% actually harbor micrometastatic disease in the putatively normal retroperitoneal lymph nodes (vs. 10-15% for seminomas)
- For this reason, these patients are generally advised to undergo a retroperitoneal lymph node dissection (RPLND). In most cases, that operation can be performed with the intent of sparing most (or all) of the lumbar sympathetic nerves (L1-4)
- If transected or removed, the patient will be unable to ejaculate (but erections are normal)
- If that staging node dissection is negative for metastatic disease, no further treatment is required except for close monitoring
- If metastases are detected, the patient is generally treated with observation (if less than or equal to 5 nodes are +, none greater than 2 cm) or two cycles of PEB chemotherapy (6 or more nodes +, any node is greater than 2 cm, or there is evidence of extranodal extension)
14
Q
What patients with NSGCTs can be followed?
A
- Selected patients with presumed clinical stage 1 disease may be candidates for surveillance
- Their tumors should not exhibit adverse phenotypes, which include vascular invasion, lymphatic invasion, high volume EC, and a high proliferative index (MIB-1 staining for Ki-67 antigen)
- Currently, primary chemotherapy (2 cycles of BEP, 2-3% relapse rate) is not recommended for most patients with high-risk clinical stage 1 NSGCT
- The superiority of preemptive chemotherapy has not been definitively proven (but has become increasingly popular in Europe) and can cause significant long-term sequelae, including infertility, a predisposition to second malignancies, and cardiovascular/neurologic toxicity
- The patient should be offered the option of semen cryopreservation prior to RPLND, radiotherapy, or the initiation of chemotherapy
15
Q
What is the management of advanced stage testis tumors?
A
- Regardless of tumor histology, all patients presenting with stage III disease receive 3-4 cycles of PEB chemotherapy
- A prognostic factor-based staging system for metastatic germ cell cancers has been formulated by the International Germ Cell Consensus Conference and is depicted in Appendix A
- Surgical resection of residual disease (>3 cm) may be required in patients with tumors who have achieved normal serum tumor-marker status following chemotherapy
- Post-chemotherapy RPLND is recommended for: (1) all patients with teratoma-positive primary tumor who achieve a serologic CR but demonstrate less than 90% radiographic regression
- Patients who achieve serologic and radiographic CRs should undergo surveillance without surgical intervention
