Campbell-Walsh Urology, 11th Edition

PART VI

Male Genitalia

37

Tumors of the Penis

Curtis A. Pettaway; Raymond S. Lance; John W. Davis

Questions

  1. Which of the following penile lesions does NOT have malignant potential?
  2. Balanitis xerotica obliterans
  3. Condylomata acuminatum
  4. Coronal papillae
  5. Bowen disease
  6. Leukoplakia
  7. Which of the following infections is associated with cervical dysplasia?
  8. Human immunodeficiency virus (HIV) infection
  9. Herpesvirus infection
  10. Gonorrhea
  11. Human papillomavirus (HPV) infection
  12. Lymphogranuloma venereum
  13. What is the major difference between Bowen disease and erythroplasia of Queyrat?
  14. Loss of rete pegs
  15. Keratin staining
  16. Viral etiologic agents
  17. Location
  18. Treatment options
  19. Kaposi sarcoma of the acquired immunodeficiency syndrome (AIDS)-related (epidemic) type is associated with which of the following etiologic agents?
  20. HPV type 16
  21. Human herpesvirus (HHV) type 8
  22. HPV type 32
  23. Haemophilus ducreyi(chancroid [soft chancre])
  24. Coxsackievirus type 23
  25. Where do penile cancers most commonly arise?
  26. Glans
  27. Shaft
  28. Frenulum
  29. Coronal sulcus
  30. Scrotum
  31. Which of the following is not considered a risk factor for the development of squamous cell carcinoma of the penis?
  32. Cigarette smoke
  33. HPV infection
  34. Phimosis
  35. Gonorrhea
  36. Chewing tobacco
  37. All of the following are preventive strategies to decrease the incidence of penile cancer EXCEPT:
  38. circumcision after 21 years of age.
  39. avoiding sexual promiscuity.
  40. daily genital hygiene.
  41. avoiding cigarette smoke.
  42. circumcision before puberty.
  43. Which of the following statements regarding penile cancer is FALSE?
  44. Cancer may develop anywhere on the penis.
  45. Because of the associated discomfort, patients usually present to physicians within the first month of noting the lesion.
  46. Phimosis may obscure the nature of the lesion.
  47. Penetration of the Buck fascia and the tunica albuginea by the tumor permits invasion of the vascular corpora.
  48. Cancer cells reach the contralateral inguinal region because of lymphatic cross-communications at the base of the penis.
  49. Before a treatment plan for penile cancer is initiated, which of the following is TRUE?
  50. Adequate biopsies to determine stage are unimportant because all patients should be treated with amputation.
  51. Radiologic studies play no role in decision making.
  52. DNA flow cytometry should be performed on virtually all specimens because it provides crucial information.
  53. Tumor stage, grade, and vascular invasion status all provide prognostically important information.
  54. No disfiguring therapy is indicated, because spontaneous remissions have been noted in approximately 10% of cases.
  55. Which of the following statements is TRUE regarding the natural history of penile cancer?
  56. Metastases from the primary tumor often involve lung, liver, or bone as initial sites.
  57. Lymphatic drainage from the primary tumor is ipsilateral alone in most cases.
  58. Metastasis often initially involves spread from the corpora cavernosa to the pelvic lymph nodes.
  59. Metastasis initially involves inguinal lymph nodes beneath the fascia lata.
  60. Metastasis initially involves inguinal lymph nodes above the fascia lata.
  61. Which of the following statements concerning hypercalcemia in patients with penile cancer is TRUE?
  62. It is more commonly due to massive bone metastases than bulky soft tissue metastases.
  63. It is often related to uremia due to ureteral obstruction.
  64. It may be due to the action of parathyroid hormone-like substances released from the tumor.
  65. It is related to the action of osteoblasts on bone formation.
  66. It is managed with aggressive diuretic administration as first-line therapy.
  67. The following statements are true regarding imaging tests in patients with penile cancer EXCEPT:
  68. Both ultrasonography and magnetic resonance imaging (MRI) lack sensitivity for the detection of corpus cavernosum involvement.
  69. Computed tomography (CT) is not an appropriate test for determining primary tumor stage.
  70. CT may be beneficial in detecting enlarged inguinal nodes in obese patients or those who have had prior inguinal therapy.
  71. Lymphangiography can detect abnormal architecture in normal-sized lymph nodes.
  72. Inguinal palpation is preferred to CT and lymphangiography for determining inguinal nodal status.
  73. According to the 2010 version of the International Union Against Cancer/TNM staging system for penile cancer, which of the following statements is TRUE?
  74. Primary tumor stage is based on the size of the primary lesion.
  75. Lymph node stage is based on the resectability of involved nodes.
  76. Stage T2 tumors are based on biopsy and involve corpora cavernosa only.
  77. Large verrucous carcinomas are considered stage Ta.
  78. Stage T1 tumors may involve the urethra at the meatus.
  79. What is the strongest prognostic factor for survival in penile cancer?
  80. The presence of lymph node metastasis
  81. The grade of the primary tumor
  82. The stage of the primary tumor
  83. Vascular invasion presence in the primary tumor
  84. The extent of lymph node metastasis
  85. Criteria for curative surgical resection (> 70% 5-year survival) in patients treated for lymph node metastasis include all of the following EXCEPT:
  86. no more than two positive inguinal lymph nodes.
  87. no positive pelvic lymph nodes.
  88. absence of extranodal extension of cancer.
  89. unilateral metastasis.
  90. a single metastasis of only 6 cm.
  91. Surgical staging of the inguinal region is strongly considered under all of the following conditions EXCEPT:
  92. palpable adenopathy.
  93. stage T2 or greater primary tumor.
  94. presence of vascular invasion in primary tumor.
  95. presence of predominantly high-grade cancer in primary tumor.
  96. stage Ta tumors.
  97. A watchful waiting strategy toward the management of the inguinal region in patients with no palpable adenopathy is recommended for all of the following situations EXCEPT:
  98. primary tumor stage Tis.
  99. primary tumor stage Ta.
  100. primary tumor stage T1, grade I.
  101. primary tumor stage T1, grade II.
  102. noncompliant patients.
  103. Strategies to minimize the morbidity of inguinal staging in patients with no palpable adenopathy include all the following EXCEPT:
  104. superficial inguinal lymph node dissection.
  105. modified complete inguinal dissection.
  106. standard ilioinguinal dissection.
  107. sentinel lymph node biopsy.
  108. dynamic sentinel node biopsy.
  109. Which of the following inguinal staging procedures is considered the "gold standard" for detecting microscopic metastases while limiting both morbidity and false-negative findings?
  110. Inguinal node biopsy
  111. Superficial inguinal dissection
  112. Sentinel lymph node dissection
  113. Fine-needle aspiration cytology
  114. Sentinel lymph node biopsy
  115. For patients with proven unilateral metastasis involving 2 or more lymph nodes at presentation, all of the following surgical considerations are true EXCEPT:
  116. Ipsilateral ilioinguinal lymphadenectomy should be performed.
  117. A contralateral staging procedure is not indicated.
  118. A contralateral staging procedure is indicated.
  119. Both a superficial dissection and a deep ipsilateral dissection are performed.
  120. Ipsilateral pelvic dissection provides useful prognostic information.
  121. Adjuvant or neoadjuvant chemotherapy should be considered in addition to surgery for all of the following EXCEPT:
  122. single pelvic nodal metastasis.
  123. extranodal extension of cancer.
  124. fixed inguinal masses.
  125. two unilateral inguinal nodes with focal metastases.
  126. single 6-cm inguinal lymph node.
  127. The majority of penile cancers are histologically:
  128. melanoma.
  129. bowenoid papulosis.
  130. squamous cell carcinoma.
  131. epidemic Kaposi sarcoma.
  132. verrucous carcinoma.
  133. Which of the following chemotherapeutic agents used in combination therapy for penile cancer has been associated with significant pulmonary toxicity?
  134. Bleomycin
  135. Methotrexate
  136. Cisplatin
  137. 5-Fluorouracil (5-FU)
  138. Paclitaxel
  139. Indications for radiation therapy as primary treatment for penile cancer include which of the following?
  140. Young, sexually active patient with a small lesion
  141. Patient refuses surgery
  142. Patient with inoperable tumor who needs local treatment but desires to retain the penis
  143. None of the above
  144. a, b, and c
  145. Primary penile melanoma is thought to be rare for what reason?
  146. Penile skin is protected from exposure to the sun
  147. Keratin content in penile skin is decreased
  148. Penile blood supply precludes such tumor development
  149. Effective topical chemotherapy exists
  150. None of the above
  151. Lymphomatous infiltration of the penis is most likely secondary to which condition?
  152. Autoimmune disorder
  153. Diffuse disease
  154. Metastasis from a distant primary tumor
  155. Chronic infection
  156. Previous venereal infection
  157. What is the most frequently encountered sign of metastatic involvement of the penis?
  158. Pain
  159. Urethral discharge
  160. Ecchymoses
  161. Priapism
  162. Preputial swelling
  163. Which of the following features of Buschke-Löwenstein tumor characterizes it as different from condyloma acuminatum?
  164. Propensity for early distant metastasis
  165. Disruption of the rete pegs
  166. Loss of pigmentation
  167. Autoamputation
  168. Invasion and destruction of adjacent tissues by compression
  169. Which of the following statements about how verrucous carcinoma of the penis differs from classic Buschke-Löwenstein tumor is TRUE?
  170. The terms describe the same disease.
  171. Verrucous carcinoma sometimes exhibits spontaneous regression.
  172. Proportion of melanin pigment in verrucous carcinoma is higher than in Buschke-Löwenstein tumor.
  173. Simultaneous bilateral inguinal metastases occur commonly with Buschke-Löwenstein tumor.
  174. Circumcision is not protective for verrucous carcinoma.
  175. Small lesions of erythroplasia of Queyrat may be successfully treated with which of the following?
  176. Topical 5% 5-FU
  177. Neodymium:yttrium-aluminum-garnet (Nd:YAG) laser
  178. Local excision
  179. External-beam radiation therapy
  180. All of the above

Pathology

  1. A 65-year-old man has a cauliflower-type lesion on his foreskin involving a 3-mm area of the dorsal glans. He is sexually active. The lesion is biopsied and depicted in Figure 37-1. The pathology report is verrucous carcinoma, invasive. The most appropriate treatment is:

FIGURE 37-1 (From Bostwick D, Cheng L. Urologic surgical pathology. 2nd ed. Philadelphia, PA: Elsevier; 2008.)

  1. topical 5-FU cream.
  2. laser photocoagulation.
  3. circumcision and hemiglansectomy.
  4. partial penectomy followed by bilateral groin dissection.
  5. total penectomy.
  6. A 55-year-old man has a red raised 2 × 3 mm lesion on his dorsal corona that has been present for the past 6 months. The lesion is biopsied and depicted in Figure 37-2. The diagnosis is well-differentiated squamous cell carcinoma with superficial invasion. The patient is sexually active and is very concerned about the appearance of his penis. The treatment most consistent with the patient's wishes and excellent cancer control is:

FIGURE 37-2 (From Bostwick D, Cheng L. Urologic surgical pathology. 3rd ed. Philadelphia, PA: Elsevier; 2014.)

  1. Hemiglansectomy.
  2. External beam radiation therapy.
  3. 5-FU cream application.
  4. Laser photocoagulation.
  5. Partial penectomy.

Answers

  1. c. Coronal papillae.Coronal papillae present as linear, curved, or irregular rows of conical or globular excrescences, varying from white to yellow to red, arranged along the coronal sulcus. They are considered acral angiofibromas. These lesions have not been associated with malignancy.
  2. d. Human papillomavirus (HPV) infection.HPV is recognized as the principal etiologic agent in cervical dysplasia and cervical cancer.
  3. d. Location. Carcinoma in situ of the penis is referred to by urologists and dermatologists as erythroplasia of Queyrat if it involves the glans penis or prepuce and as Bowen disease if it involves the remainder of the penile shaft skin, genitalia, or perineal region.
  4. b. Human herpesvirus (HHV) type 8.HHV type 8—also known as Kaposi sarcoma-associated herpesvirus—is strongly suspected to be the etiologic agent of epidemic (AIDS-related) Kaposi sarcoma.
  5. a. Glans.Penile tumors may present anywhere on the penis but occur most commonly on the glans (48%) and prepuce (21%).
  6. d. Gonorrhea.No convincing evidence has been found linking penile cancer to other factors such as occupation, other venereal diseases (gonorrhea, syphilis, herpes), marijuana use, or alcohol intake.
  7. a. Circumcision after 21 years of age. Adult circumcision appears to offer little or no protection from subsequent development of the disease.These data suggest that the crucial period of exposure to certain etiologic agents may have already occurred at puberty and certainly by adult age, rendering later circumcision relatively ineffective as a prophylactic tool for penile cancer.
  8. b. Because of the associated discomfort, patients usually present to physicians within the first month of noting the lesion. Patients with cancer of the penis, more than patients with other types of cancer, seem to delay seeking medical attention.In large series, from 15% to 50% of patients have been noted to delay medical care for more than a year.
  9. d. Tumor stage, grade, and vascular invasion status all provide prognostically important information.Confirmation of the diagnosis of carcinoma of the penis, an assessment of the depth of invasion and tumor grade by the combination of an adequate biopsy, and complete clinical assessment are beneficial before the initiation of definitive therapy. Biopsy can be performed as a frozen section immediately before definitive therapy in some cases.
  10. e. Metastasis initially involves inguinal lymph nodes above the fascia lata.The lymphatics of the prepuce form a connecting network that joins with the lymphatics from the skin of the shaft. These tributaries drain into the superficial inguinal nodes (the nodes external to the fascia lata).
  11. c. It may be due to the action of parathyroid hormone-like substances released from the tumor.Parathyroid hormone and related substances may be produced by both tumor and metastases that activate osteoclastic bone resorption.
  12. a. Both ultrasonography and magnetic resonance imaging (MRI) lack sensitivity for the detection of corpus cavernosum involvement.The sensitivity of ultrasonography for detecting cavernosum invasion was 100% in one study. This study confirmed the value of ultrasonography in assessing the primary tumor also reported by other investigators. For lesions suspected of invading the corpus cavernosum, both ultrasonography and contrast-enhanced MRI may provide unique information, especially when organ-sparing surgery is considered.
  13. d. Large verrucous carcinomas are considered stage Ta.According to this staging system, designations for primary tumors are as follows: Tx indicates that the primary tumor cannot be assessed; T0 indicates no evidence of tumor; Tis indicates carcinoma in situ; Ta indicates noninvasive verrucous carcinoma; T1 indicates tumor invading subepithelial connective tissue; T2 indicates tumor invading corpus spongiosum or cavernosum; T3 indicates tumor invading urethra or prostate; and T4 indicates tumor invading other adjacent structures.
  14. e. The extent of lymph node metastasis. The presence and extent of metastasis to the inguinal region are the most important prognostic factors for survival in patients with squamous penile cancer.
  15. e. A single metastasis of only 6 cm. Pathologic criteria associated with long-term survival after attempted curative surgical resection of inguinal metastases (i.e., 80% 5-year survival) include (1) minimal nodal disease (up to two involved nodes in most series), (2) unilateral involvement, (3) no evidence of extranodal extension of cancer, and (4) the absence of pelvic nodal metastases.A lymph node larger than 4 cm is often associated with extranodal extension of cancer.
  16. e. stage Ta tumors.Tumor histologic type associated with little or no risk for metastasis includes those patients with primary tumors exhibiting (1) carcinoma in situ or (2) verrucous carcinoma.
  17. e. noncompliant patients.Noncompliant patients with any degree of invasion in the primary tumor specimen should have an inguinal staging procedure recommended.
  18. c. standard ilioinguinal dissection.In patients with no evidence of palpable adenopathy who are selected to undergo inguinal procedures by virtue of adverse prognostic factors within the primary tumor, the goal is to define whether metastases exist with minimal morbidity for the patient. A variety of treatment options for this purpose have been reported and include (1) fine-needle aspiration cytology, (2) node biopsy, (3) sentinel lymph node biopsy, (4) extended sentinel lymph node dissection, (5) dynamic sentinel node biopsy, (6) superficial dissection, and (7) modified complete dissection.
  19. b. Superficial inguinal dissection.One series found that the sensitivity of fine-needle aspiration cytology was approximately 71% in 18 patients with clinically negative lymph nodes. This finding and the technical difficulty with lymphangiography make aspiration less practical as a staging technique for patients with no palpable lymph nodes. Biopsies directed to a specific anatomic area can be unreliable in identifying microscopic metastasis and are no longer recommended.
  20. b. A contralateral staging procedure is not indicated.Support for a bilateral procedure is based on the finding of bilateral lymphatic drainage from the primary site in the majority of cases and contralateral metastases in more than 50% of patients so treated in some series, even if the contralateral nodal region was negative to palpation.
  21. d. two unilateral inguinal nodes with focal metastases.For patients requiring ilioinguinal lymphadenectomy because of the presence of metastases, adjuvant chemotherapy should be considered for those exhibiting more than two positive lymph nodes, extranodal extension of cancer, or pelvic nodal metastasis. Reports from one center further confirmed the value of adjuvant chemotherapy. Of 25 node-positive patients treated with adjuvant combination vincristine-bleomycin-methotrexate chemotherapy, 82% survived 5 years, compared with 37% of 31 patients treated with surgery alone.
  22. c. squamous cell carcinoma.The majority of tumors of the penis are squamous cell carcinomas demonstrating keratinization, epithelial pearl formation, and various degrees of mitotic activity.
  23. a. Bleomycin.Response rates of bleomycin, whether as a single agent or in combination with other agents, has not been shown to be superior to cisplatin alone, but has been associated with significant pulmonary toxicity and death in several series of patients treated for metastatic penile cancer.
  24. e. a, b, and c.Radiation therapy may be considered in a select group of patients: (1) young individuals presenting with small (2 to 4 cm), superficial, exophytic, noninvasive lesions on the glans or coronal sulcus; (2) patients who refuse as an initial form of treatment; and (3) patients with inoperable tumor or distant metastases who require local therapy to the primary tumor but who express a desire to retain the penis.
  25. a. Penile skin is protected from exposure to the sun. Melanoma and basal cell carcinoma rarely occur on the penis, presumably because the organ's skin is protected from exposure to the sun.
  26. b. Diffuse disease.When lymphomatous infiltration of the penis is diagnosed, a thorough search for systemic disease is necessary.
  27. d. Priapism.The most frequent sign of penile metastasis is priapism; penile swelling, nodularity, and ulceration have also been reported.
  28. e. Invasion and destruction of adjacent tissues by compression.The Buschke-Löwenstein tumor differs from condyloma acuminatum in that condylomata, regardless of size, always remain superficial and never invade adjacent tissue. Buschke-Löwenstein tumor displaces, invades, and destroys adjacent structures by compression. Aside from this unrestrained local growth, it demonstrates no signs of malignant change on histologic examination and does not metastasize.
  29. a. The terms describe the same disease.Buschke-Löwenstein tumor is synonymous with verrucous carcinoma and giant condyloma acuminatum.
  30. e. All of the above.When lesions are small and noninvasive, local excision, which spares penile anatomy and function, is satisfactory. Circumcision will adequately treat preputial lesions. Fulguration may be successful but often results in recurrences. Radiation therapy has successfully eradicated these tumors, and well-planned, appropriately delivered radiation results in minimal morbidity. Topical 5-FU as the 5% base causes denudation of malignant and premalignant areas while preserving normal skin. There are also reports of successful treatment with Nd:YAG laser.

Pathology

  1. c. Circumcision and hemiglansectomy.Verrucous carcinoma is locally invasive but normally does not metastasize. Note invasion at the base in the figure. Thus wide local excision is indicated.
  2. a. Hemiglansectomy.Wide local excision of the well-differentiated superficially invasive (T1) squamous cell carcinoma will provide excellent cancer control while providing the best cosmetic result. Moreover, the permanent pathology will be very helpfuul in follow-up and prognosis.

Chapter review

  1. Pearly penile papules or papillomas are normal and generally found on the glans penis or corona.
  2. Zoon balanitis presents as an erythematous plaque that pathologically reveals a plasma cell infiltrate and is cured by circumcision. Grossly, it is difficult to distinguish from carcinoma in situ.
  3. Lesions associated with the development of penile cancer include cutaneous horn, balanitis xerotica obliterans, and pseudoepitheliomatous micaceous and keratotic balanitis.
  4. Bowenoid papulosis meets all the histologic criteria for carcinoma in situ; however, the course is invariably benign.
  5. Kaposi sarcoma is classified as (1) not associated with immunodeficiency and with an indolent and rarely fatal course, (2) associated with immunosuppressive treatment that is often reversed by modification of the immunosuppressive medications, (3) African Kaposi sarcoma that may be either indolent or aggressive, and (4) HIV-related Kaposi sarcoma. If surgical treatment is required, localized excision is often successful.
  6. Carcinoma in situ of the glans is called erythroplasia of Queyrat; if carcinoma in situ is on the shaft of the penis it is called Bowen disease.
  7. On the penis there are multiple cross-connections of lymphatics so that drainage can occur to either inguinal region.
  8. The overwhelming majority of penile squamous cell carcinomas occur on the glans, the prepuce, or corona.
  9. Vascular invasion and perineural invasions are strong predictors of lymph node metastases. Distant metastases occur late in the course of the disease and are rare without recognized significant inguinal and pelvic lymphadenopathy.
  10. Tis, TA, T1, grade 1 and grade 2 tumors are at low risk for metastases.
  11. T2 or greater and grade 3 tumors have a greater than 50% incidence of metastases.
  12. The criteria associated with long-term survival after inguinal lymphadenectomy include (1) minimal nodal disease, (2) unilateral involvement, (3) no evidence of extranodal extension, and (4) absence of pelvic node metastases.
  13. Inguinal lymphadenectomy should be bilateral when performed on patients at initial presentation. If, on the other hand, the patient presents with unilateral adenopathy at a prolonged time after the initial presentation and treatment of the primary lesion, a unilateral inguinal node dissection may be considered.
  14. HPV 16, 18, 31, and 33 are associated with carcinoma in situ and invasive squamous cell cancer.
  15. Tumor grade correlates with microscopic contiguous spread: 5 mm for grade 1 and 2 and 10 mm for grade 3. Skip lesions generally do not occur.
  16. There is an improved survival when lymphadenectomy is done early for nonpalpable microscopic disease as opposed to delaying it until the nodes become palpable. When the inguinal nodes are negative, the ipsilateral pelvic nodes are almost always negative as well.
  17. Before radiation therapy, the patient should be circumcised.
  18. Advanced disease may benefit from cisplatin-based combination chemotherapy.
  19. Tx indicates that the primary tumor cannot be assessed; T0 indicates no evidence of tumor; Tis indicates carcinoma in situ; Ta indicates noninvasive verrucous carcinoma; T1 indicates tumor invading subepithelial connective tissue; T2 indicates tumor invading corpus spongiosum or cavernosum; T3 indicates tumor invading urethra or prostate; and T4 indicates tumor invading other adjacent structures.
  20. The Buschke-Löwenstein tumor differs from condyloma acuminatum in that condylomata, regardless of size, always remain superficial and never invade adjacent tissue. Buschke-Löwenstein tumor displaces, invades, and destroys adjacent structures by compression. Aside from this unrestrained local growth, it demonstrates no signs of malignant change on histologic examination and does not metastasize.