Penile%20cancer Diagnosis
Diagnosis
Physical Examination
- Examine for physical signs of advanced disease (eg palpable nodes, hepatomegaly) aside from constitutional symptoms in the history (eg fatigue, weight loss, cachexia, confusion, pain)
- Description of the primary tumor of a suspected penile cancer must include the following:
- Color, number, diameter, location, boundary, morphology (eg flat, nodular, papillary or ulcerous) of the lesion
- Relationship of the lesion to other structures (eg corpus cavernosum, corpus spongiosum, submucosa, tunica albuginea, & urethra); physical examination can determine tumor infiltration into the corpora cavernosa
- Penile length
- Assess extent of local invasion by palpating penis
- As penile cancer primarily drains to the inguinal nodes, palpate both groins if the lymph nodes are palpable or not
- If palpable, note the characteristics of the nodes: Diameter, unilateral or bilateral localization, number of nodes on each side, relationship to other structures, eg mobility or fixation to adjacent structures or involvement of overlying skin
- Palpable lymph nodes are highly suspicious for metastases to lymph nodes while nonpalpable nodes have a 25% possibility of micrometastatic disease; thus, perform an invasive pathologic lymph node staging in high-risk patients with nonpalpable lymph nodes
Laboratory Tests
- A serum calcium should be included in the routine lab tests to check for tumor-induced hypercalcemia
- Penile cancer has no established tumor marker
- Squamous cell carcinoma antigen is not a sensitive marker of tumor burden & is currently not useful in clinical practice
Penile Biopsy
- A cytological &/or histological diagnosis should be made of the penile lesion via excisional, incisional or punch biopsy
- A punch biopsy may be adequate for superficial lesions; however, an excisional biopsy is preferred because it can properly determine the depth of invasion & stage
- Result will show grade of the tumor, will aid in patient’s risk stratification for involvement of regional lymph nodes, & will determine treatment approach based on a pathologic diagnosis
Imaging
- Ultrasound can show infiltration of the corpora or enlargement of inguinal nodes
- Magnetic resonance imaging (MRI) scan with intracavernosal injection of prostaglandin E1 can help detect invasion into the corpora cavernosa & assess if limited surgery is possible
- MRI & computed tomography (CT) scans can detect inguinal & pelvic node enlargement
- Above imaging studies are especially performed in patients with a large body mass index (BMI) or who have undergone a previous inguinal procedure due to the limitation of PE in these circumstances
- Routine diagnostic imaging for assessment of metastases should only be done with bulky regional nodal metastases, eg CT of chest, abdomen & pelvis, as reliable detection of micrometastases cannot be performed with conventional CT or MRI scans
- For regional (inguinal & pelvic nodes) & more distant metastases, a positron emission tomography (PET)/CT scan can be performed in patients with positive inguinal nodes
- 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET/CT) scan can accurately detect pelvic lymph node metastases & more distant metastases in palpable inguinal node-positive penile cancer
- A bone or brain scan may be indicated in symptomatic patients for detection of distant metastases
Staging
- The staging system together with tumor grade is the most simple & accurate way of predicting cancer-specific mortality for penile cancer after excision of primary tumor
- Surgical staging of the groin [eg fine-needle aspiration (FNA), dynamic sentinel node biopsy (DSNB), or inguinal lymph node dissection (ILND)] would depend on the features of the primary tumor & the presence or absence of palpable inguinal lymph nodes
- Risk factors for lymph node metastasis include anatomical site, growth pattern, invasion of perineural spaces, irregular front of invasion, lymphovascular invasion, pathological subtypes, positive margins of resection, size of the primary tumor, tumor depth or thickness (tumor grade), & urethral invasion
- Strongest predictors of penile cancer metastasis & a poor prognosis are a high histological grade & perineural & lymphovascular invasion
- The most important prognostic factor for overall survival is the presence & extent of metastases to the inguinal nodes which include inguinal lymph node involvement, number & site of positive nodes, & involvement of extracapsular nodes
- Patients with nonpalpable inguinal lymphadenopathy can be grouped prognostically based on the likelihood of having an occult node-positive disease with risk stratified based on primary tumor: Low risk (Tis, TaG1-2 or T1G1), intermediate risk (T1G2), & high risk (≥T2 or any G3 or G4)
- Recent data suggest that high-risk human papilloma virus deoxyribonucleic acid (HPV DNA) expression in tumors is associated with a survival benefit as it does not appear to be related with lymph node metastasis
TNM Classification for Penile Cancer According to the American Joint Committee on Cancer (AJCC) (2010, 7th ed)
T |
Primary tumor |
TX |
Primary tumor cannot be assessed |
T0 |
Primary tumor not evident |
Ta |
Non-invasive verrucous carcinoma not associated with destructive invasion |
Tis |
Carcinoma in situ |
T1a |
Tumor invades subepithelial connective tissue without lymphovascular invasion & is well or moderately differentiated (T1G1-2) |
T1b |
Tumor invades subepithelial connective tissue with lymphovascular invasion or is poorly differentiated or undifferentiated (T1G3-4) |
T2 |
Tumor invades corpus cavernosum or spongiosum |
T3 |
Tumor invades urethra |
T4 |
Tumor invades adjacent structures |
Regional lymph nodes |
|
N |
Clinical |
NX |
Regional lymph nodes cannot be assessed |
N0 |
No palpable or visibly enlarged lymph node |
N1 |
Inguinal lymph node is palpable, mobile, unilateral |
N2 |
Inguinal lymph nodes are palpable, mobile, multiple, or bilateral |
N3 |
Palpable fixed inguinal nodal mass or pelvic lymphadenopathy unilateral or bilateral |
pN |
Pathologic1 |
pNX |
Regional lymph nodes cannot be assessed |
pN0 |
No metastasis to regional lymph node |
pN1 |
Metastasis in a single inguinal node |
pN2 |
Metastases in multiple or bilateral inguinal lymph nodes |
pN3 |
Extranodal extension of lymph node metastasis or pelvic lymph node(s) unilateral or bilateral |
M |
Distant metastasis |
M0 |
No distant metastasis |
M1 |
Distant metastasis |
G |
Histopathological grading |
GX |
Grade of differentiation cannot be assessed |
G1 |
Well differentiated |
G2 |
Moderately differentiated |
G3-4 |
Poorly differentiated/undifferentiated |
1The pN categories are based upon biopsy or surgical excision
Anatomic Stage/Prognostic Group for Penile Cancer
Stage 0 |
Tis Ta |
N0 |
M0 |
Stage I |
T1a |
N0 |
M0 |
Stage II |
T1b |
N0 |
M0 |
Stage III A |
T1-3 |
N1 |
M0 |
Stage III B |
T1-3 |
N2 |
M0 |
Stage IV |
T4 |
Any N |
M0 |