Penile Cancer

Overview

Epidemiology

• Overall, penile malignancies are rare. 
• Highest incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency: age group 50–70 years 
• In the United States:
  • Estimated annual incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency of approximately 2000 new cases 
  • Average incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency: 1 in 100,000 men per year
• In highly industrial countries (United States, Europe, Canada), annual incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency rates are lower. 
• Prevalence Prevalence The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. Measures of Disease Frequency rates are 5–10 times higher in nonindustrialized countries.

Risk factors

• Uncircumcised males:
  • Greatest risk contributing to malignant penile lesions 
  • 22-fold increased risk versus circumcised males 
  • Maximal risk reduction of penile cancer with circumcision Circumcision Excision of the prepuce of the penis (foreskin) or part of it. HIV Infection and AIDS performed in the neonatal period  
• History of HPV HPV Human papillomavirus (HPV) is a nonenveloped, circular, double-stranded DNA virus belonging to the Papillomaviridae family. Humans are the only reservoir, and transmission occurs through close skin-to-skin or sexual contact. Human papillomaviruses infect basal epithelial cells and can affect cell-regulatory proteins to result in cell proliferation. Papillomavirus (HPV) or HIV infection HIV infection Human immunodeficiency virus (HIV), a single-stranded RNA virus belonging to the Retroviridae family, is the etiologic agent of acquired immunodeficiency syndrome (AIDS). The human immunodeficiency virus is a sexually transmitted or blood-borne infection that attacks CD4+ T lymphocyte cells, macrophages, and dendritic cells, leading to eventual immunodeficiency. HIV Infection and AIDS: 
  • 8-fold increase of penile lesions 
  • Up to 50% of penile cancers are associated with HPV HPV Human papillomavirus (HPV) is a nonenveloped, circular, double-stranded DNA virus belonging to the Papillomaviridae family. Humans are the only reservoir, and transmission occurs through close skin-to-skin or sexual contact. Human papillomaviruses infect basal epithelial cells and can affect cell-regulatory proteins to result in cell proliferation. Papillomavirus (HPV) serotypes 16 (most common), 6, and 18. 
  • Particularly increased risk of basaloid and warty penile carcinomas 
• HIV HIV Anti-HIV Drugs
• Lower socioeconomic status 
• Poor genital hygiene (accumulation of smegma)
• Smoking Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases 
• Psoralens and ultraviolet A photochemotherapy
• Chronic inflammatory conditions: 
  • Phimosis Phimosis A condition in which the foreskin cannot be retracted to reveal the glans penis. It is due to tightness or narrowing of the foreskin opening. Penile Anomalies and Conditions 
  • Balanitis Balanitis Inflammation of the head of the penis, glans penis. Penile Anomalies and Conditions

Pathophysiology

Anatomy

• Most cancers of the penis Penis The penis is the male organ of copulation and micturition. The organ is composed of a root, body, and glans. The root is attached to the pubic bone by the crura penis. The body consists of the 2 parallel corpora cavernosa and the corpus spongiosum. The glans is ensheathed by the prepuce or foreskin. Penis: Anatomy arise from the squamous epithelium Epithelium The epithelium is a complex of specialized cellular organizations arranged into sheets and lining cavities and covering the surfaces of the body. The cells exhibit polarity, having an apical and a basal pole. Structures important for the epithelial integrity and function involve the basement membrane, the semipermeable sheet on which the cells rest, and interdigitations, as well as cellular junctions. Surface Epithelium: Histology of the epidermis Epidermis The external, nonvascular layer of the skin. It is made up, from within outward, of five layers of epithelium: (1) basal layer (stratum basale epidermidis); (2) spinous layer (stratum spinosum epidermidis); (3) granular layer (stratum granulosum epidermidis); (4) clear layer (stratum lucidum epidermidis); and (5) horny layer (stratum corneum epidermidis). Skin: Structure and Functions and dermis Dermis A layer of vascularized connective tissue underneath the epidermis. The surface of the dermis contains innervated papillae. Embedded in or beneath the dermis are sweat glands; hair follicles; and sebaceous glands. Skin: Structure and Functions. 
• Two distinct fascial layers arise beneath the penile shaft Penile Shaft Bowen Disease and Erythroplasia of Queyrat skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions:
  • Superficial dartos fascia Fascia Layers of connective tissue of variable thickness. The superficial fascia is found immediately below the skin; the deep fascia invests muscles, nerves, and other organs. Cellulitis 
  • Deep (Buck’s) fascia Fascia Layers of connective tissue of variable thickness. The superficial fascia is found immediately below the skin; the deep fascia invests muscles, nerves, and other organs. Cellulitis 
• Within Bucks fascia Fascia Layers of connective tissue of variable thickness. The superficial fascia is found immediately below the skin; the deep fascia invests muscles, nerves, and other organs. Cellulitis are the two cavernosal bodies dorsally and the solitary spongiosum ventrally. 
• Lymphatic drainage of the penis Penis The penis is the male organ of copulation and micturition. The organ is composed of a root, body, and glans. The root is attached to the pubic bone by the crura penis. The body consists of the 2 parallel corpora cavernosa and the corpus spongiosum. The glans is ensheathed by the prepuce or foreskin. Penis: Anatomy is mainly via the inguinal lymph Lymph The interstitial fluid that is in the lymphatic system. Secondary Lymphatic Organs nodes in the groin Groin The external junctural region between the lower part of the abdomen and the thigh. Male Genitourinary Examination:
  • No pattern of laterality for drainage, with much crossover 
  • Superficial and deep lymphatics, either above or below the fascia Fascia Layers of connective tissue of variable thickness. The superficial fascia is found immediately below the skin; the deep fascia invests muscles, nerves, and other organs. Cellulitis lata

Pathogenesis and pathology

• Cancer growth:
  • Small lesions initially, often noted on the glans or prepuce Prepuce The double-layered skin fold that covers the glans penis, the head of the penis. Penis: Anatomy
  • HPV-mediated penile carcinomas: 
    • Oncoproteins E6 and E7 produced by HPV HPV Human papillomavirus (HPV) is a nonenveloped, circular, double-stranded DNA virus belonging to the Papillomaviridae family. Humans are the only reservoir, and transmission occurs through close skin-to-skin or sexual contact. Human papillomaviruses infect basal epithelial cells and can affect cell-regulatory proteins to result in cell proliferation. Papillomavirus (HPV) infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease can interfere with tumor Tumor Inflammation suppressor gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics function.
    • Alterations of the RB1 and p53 genetic pathways and cell-cycle regulators p21 and p16 occur.
• Carcinoma in situ Carcinoma in situ A lesion with cytological characteristics associated with invasive carcinoma but the tumor cells are confined to the epithelium of origin, without invasion of the basement membrane. Leukoplakia ( CIS CIS Multiple Sclerosis) or penile intraepithelial neoplasia: 
  • Bowen disease Bowen Disease Bowen disease and erythroplasia of Queyrat are 2 related entities that describe squamous cell carcinoma (SCC) in situ of the skin. Bowen disease usually presents in sun-exposed areas (e.g., face and forearms) as a red, scaly skin lesion. When the glans penis is involved, the lesion is called erythroplasia of Queyrat, with uncircumcised males being at high risk. Bowen Disease and Erythroplasia of Queyrat presents as lesions on the penile shaft Penile Shaft Bowen Disease and Erythroplasia of Queyrat.
  • Erythroplasia of Queyrat Erythroplasia of Queyrat Bowen disease and erythroplasia of Queyrat are 2 related entities that describe squamous cell carcinoma (SCC) in situ of the skin. Bowen disease usually presents in sun-exposed areas (e.g., face and forearms) as a red, scaly skin lesion. When the glans penis is involved, the lesion is called erythroplasia of Queyrat, with uncircumcised males being at high risk. Bowen Disease and Erythroplasia of Queyrat presents with lesions on the glans. 
• Squamous cell carcinoma Squamous cell carcinoma Cutaneous squamous cell carcinoma (cSCC) is caused by malignant proliferation of atypical keratinocytes. This condition is the 2nd most common skin malignancy and usually affects sun-exposed areas of fair-skinned patients. The cancer presents as a firm, erythematous, keratotic plaque or papule. Squamous Cell Carcinoma (SCC) (SCC):
  • Common variant:
    • Comprises up to ⅔ of SCC cases
    • Typically invades the corpus spongiosum Corpus spongiosum Penis: Anatomy
    • Inguinal node Inguinal node Anal Cancer metastases are present in 25%–40% of cases. 
  • Papillary carcinoma: 2%–15% of cases
    • Usually low grade or well differentiated but superficially invasive 
    • Microscopic evidence of hyperkeratosis Hyperkeratosis Ichthyosis Vulgaris and papillomatosis 
    • Not linked to HPV HPV Human papillomavirus (HPV) is a nonenveloped, circular, double-stranded DNA virus belonging to the Papillomaviridae family. Humans are the only reservoir, and transmission occurs through close skin-to-skin or sexual contact. Human papillomaviruses infect basal epithelial cells and can affect cell-regulatory proteins to result in cell proliferation. Papillomavirus (HPV) infection 
    • Not often associated with vascular or perineural invasion 
  • Warty (condylomatous): 7%–10% of cases 
    • Cauliflower-like lesions 
    • Prominent fibrovascular core with papillomatous formations 
    • Does not commonly reach vascular and neural structures
    • Linked to HPV HPV Human papillomavirus (HPV) is a nonenveloped, circular, double-stranded DNA virus belonging to the Papillomaviridae family. Humans are the only reservoir, and transmission occurs through close skin-to-skin or sexual contact. Human papillomaviruses infect basal epithelial cells and can affect cell-regulatory proteins to result in cell proliferation. Papillomavirus (HPV) infection 
    • Inguinal node Inguinal node Anal Cancer metastasis Metastasis The transfer of a neoplasm from one organ or part of the body to another remote from the primary site. Grading, Staging, and Metastasis in 17%–25% of cases 
  • Basaloid carcinoma: 4%–10% of cases 
    • Ulcerated irregular masses related to HPV HPV Human papillomavirus (HPV) is a nonenveloped, circular, double-stranded DNA virus belonging to the Papillomaviridae family. Humans are the only reservoir, and transmission occurs through close skin-to-skin or sexual contact. Human papillomaviruses infect basal epithelial cells and can affect cell-regulatory proteins to result in cell proliferation. Papillomavirus (HPV)
    • Histologically present as uniform and small hyperchromatic cells with central necrosis Necrosis The death of cells in an organ or tissue due to disease, injury or failure of the blood supply. Ischemic Cell Damage. 
    • Usually deeply invasive into the corpus cavernosum or spongiosum 
  • Verrucous carcinoma Verrucous Carcinoma Squamous Cell Carcinoma (SCC): 3%–7% of cases 
    • Usually low grade and exophytic Exophytic Retinoblastoma
    • Histologically straight papillae Papillae Lips and Tongue: Anatomy lined by extremely well-differentiated neoplastic cells 
    • Hyperkeratotic surface with interpapillary keratin Keratin A class of fibrous proteins or scleroproteins that represents the principal constituent of epidermis; hair; nails; horny tissues, and the organic matrix of tooth enamel. Two major conformational groups have been characterized, alpha-keratin, whose peptide backbone forms a coiled-coil alpha helical structure consisting of type I keratin and a type II keratin, and beta-keratin, whose backbone forms a zigzag or pleated sheet structure. Alpha-keratins have been classified into at least 20 subtypes. In addition multiple isoforms of subtypes have been found which may be due to gene duplication. Seborrheic Keratosis 
  • Sarcomatoid (spindle cell) carcinoma: 1%–6% of cases 
    • Most aggressive variant
    • Poorly differentiated, ulcerated, or rounded polypoid masses
    • Usually with vascular and perineural invasion 
• Basal cell carcinoma Basal cell carcinoma Basal cell carcinoma is the most common skin malignancy. This cancer arises from the basal layer of the epidermis. The lesions most commonly appear on the face as pearly nodules, often with telangiectatic blood vessels and ulceration in elderly individuals. Basal Cell Carcinoma (BCC): low risk of metastasis Metastasis The transfer of a neoplasm from one organ or part of the body to another remote from the primary site. Grading, Staging, and Metastasis
• Sarcoma (including Kaposi Kaposi A multicentric, malignant neoplastic vascular proliferation characterized by the development of bluish-red cutaneous nodules, usually on the lower extremities, most often on the toes or feet, and slowly increasing in size and number and spreading to more proximal areas. The tumors have endothelium-lined channels and vascular spaces admixed with variably sized aggregates of spindle-shaped cells, and often remain confined to the skin and subcutaneous tissue, but widespread visceral involvement may occur. Hhv-8 is the suspected cause. There is also a high incidence in AIDS patients. AIDS-defining Conditions’s sarcoma, which is associated with HHV-8
• Melanoma Melanoma Melanoma is a malignant tumor arising from melanocytes, the melanin-producing cells of the epidermis. These tumors are most common in fair-skinned individuals with a history of excessive sun exposure and sunburns. Melanoma: most aggressive skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions cancer
• Metastasis Metastasis The transfer of a neoplasm from one organ or part of the body to another remote from the primary site. Grading, Staging, and Metastasis to the penis Penis The penis is the male organ of copulation and micturition. The organ is composed of a root, body, and glans. The root is attached to the pubic bone by the crura penis. The body consists of the 2 parallel corpora cavernosa and the corpus spongiosum. The glans is ensheathed by the prepuce or foreskin. Penis: Anatomy is rare.

Clinical Presentation and Diagnosis

Presentation Presentation The position or orientation of the fetus at near term or during obstetric labor, determined by its relation to the spine of the mother and the birth canal. The normal position is a vertical, cephalic presentation with the fetal vertex flexed on the neck. Normal and Abnormal Labor

• Initially presents as a skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions abnormality or palpable lesion on the penis Penis The penis is the male organ of copulation and micturition. The organ is composed of a root, body, and glans. The root is attached to the pubic bone by the crura penis. The body consists of the 2 parallel corpora cavernosa and the corpus spongiosum. The glans is ensheathed by the prepuce or foreskin. Penis: Anatomy: 
  • Majority arise from the glans penis Penis The penis is the male organ of copulation and micturition. The organ is composed of a root, body, and glans. The root is attached to the pubic bone by the crura penis. The body consists of the 2 parallel corpora cavernosa and the corpus spongiosum. The glans is ensheathed by the prepuce or foreskin. Penis: Anatomy, at the coronal Coronal Computed Tomography (CT) sulcus or on the prepuce Prepuce The double-layered skin fold that covers the glans penis, the head of the penis. Penis: Anatomy.
  • May be painful, but usually painless 
• Lesions can vary in size and characteristics: 
  • Ulcerated lesions 
  • Infiltrative with progressive growth 
• Inguinal adenopathy presents in about 30%–60% of cases. 
• Distant metastasis Metastasis The transfer of a neoplasm from one organ or part of the body to another remote from the primary site. Grading, Staging, and Metastasis: 
  • Usually means late disease presentation Presentation The position or orientation of the fetus at near term or during obstetric labor, determined by its relation to the spine of the mother and the birth canal. The normal position is a vertical, cephalic presentation with the fetal vertex flexed on the neck. Normal and Abnormal Labor 
  • Affects adjacent genitourinary organs or distant organs 
  • Present in about 1%–10% of cases

Physical exam

• Generalized constitutional exam (assess for overall performance status) 
• Focused genitourinary exam: 
  • Penile exam: 
    • Determine circumcision Circumcision Excision of the prepuce of the penis (foreskin) or part of it. HIV Infection and AIDS status.
    • Characterize size, depth, location, and features of lesion.
    • Assess for discharge, erythema Erythema Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of disease processes. Chalazion, and swelling Swelling Inflammation.  
  • Inguinal exam: 
    • Assess for inguinal lymphadenopathy Lymphadenopathy Lymphadenopathy is lymph node enlargement (> 1 cm) and is benign and self-limited in most patients. Etiologies include malignancy, infection, and autoimmune disorders, as well as iatrogenic causes such as the use of certain medications. Generalized lymphadenopathy often indicates underlying systemic disease. Lymphadenopathy. 
    • Number of palpable inguinal nodes 
    • Fixed or mobile nodes

Diagnostics

• Tissue biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma to confirm: 
  • Punch-type 
  • Incisional 
  • Excisional 
• Imaging:
  • Options:
    • Ultrasonography
    • MRI/CT
  • Functions:
    • Assesses primary tumor Tumor Inflammation stage and surgical approach 
    • Identifies invasion into the corpora cavernosa Corpora cavernosa Penis: Anatomy or spongiosa 
    • Determines regional lymph Lymph The interstitial fluid that is in the lymphatic system. Secondary Lymphatic Organs node involvement 
    • Imaging of other sites in case of metastasis Metastasis The transfer of a neoplasm from one organ or part of the body to another remote from the primary site. Grading, Staging, and Metastasis
• Staging Staging Methods which attempt to express in replicable terms the extent of the neoplasm in the patient. Grading, Staging, and Metastasis of inguinal lymph Lymph The interstitial fluid that is in the lymphatic system. Secondary Lymphatic Organs nodes: 
  • Fine-needle aspiration: 
    • Performed under local anesthesia Anesthesia A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. Anesthesiology: History and Basic Concepts with 23-gauge needle 
    • Samples clinically palpable nodes 
  • Dynamic sentinel node biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma: 
    • Involves injection of radioactive tracer dye 
    • Examines drainage of inguinal lymph Lymph The interstitial fluid that is in the lymphatic system. Secondary Lymphatic Organs nodes 
    • Allows for lymphatic mapping and sentinel node biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma 
  • Superficial inguinal lymph Lymph The interstitial fluid that is in the lymphatic system. Secondary Lymphatic Organs node dissection:
    • Provides direct information regarding suspicious nodes 
    • Performed by experienced pelvic surgeons 
    • Higher overall complication rates

Staging Staging Methods which attempt to express in replicable terms the extent of the neoplasm in the patient. Grading, Staging, and Metastasis

Management

Management options

Treatment approach

Carcinoma in situ Carcinoma in situ A lesion with cytological characteristics associated with invasive carcinoma but the tumor cells are confined to the epithelium of origin, without invasion of the basement membrane. Leukoplakia or Tis–T1:

• Topical therapy: 
  • Fluorouracil Fluorouracil A pyrimidine analog that is an antineoplastic antimetabolite. It interferes with DNA synthesis by blocking the thymidylate synthetase conversion of deoxyuridylic acid to thymidylic acid. Bowen Disease and Erythroplasia of Queyrat cream indicated for CIS CIS Multiple Sclerosis 
  • Imiquimod Imiquimod A topically-applied aminoquinoline immune modulator that induces interferon production. It is used in the treatment of external genital and perianal warts, superficial carcinoma, basal cell; and actinic keratosis. Hypertrophic and Keloid Scars cream for CIS CIS Multiple Sclerosis 
• Laser ablation: 
  • CO₂ laser commonly used 
  • For local ablation of superficial lesions 
  • Usually successful for CIS CIS Multiple Sclerosis 
• Total glans resurfacing: 
  • Removes the skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions and lamina propria Lamina propria Whipple’s Disease layers of the glans penis Penis The penis is the male organ of copulation and micturition. The organ is composed of a root, body, and glans. The root is attached to the pubic bone by the crura penis. The body consists of the 2 parallel corpora cavernosa and the corpus spongiosum. The glans is ensheathed by the prepuce or foreskin. Penis: Anatomy 
  • Followed by skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions graft Graft A piece of living tissue that is surgically transplanted Organ Transplantation placement 
  • Effective method for CIS CIS Multiple Sclerosis 
• Mohs micrographic surgery: 
  • Layer-by-layer excision of penile lesion 
  • Requires multiple procedures and coordination Coordination Cerebellar Disorders 
• Radiation Radiation Emission or propagation of acoustic waves (sound), electromagnetic energy waves (such as light; radio waves; gamma rays; or x-rays), or a stream of subatomic particles (such as electrons; neutrons; protons; or alpha particles). Osteosarcoma therapy: 
  • Via external-beam or interstitial brachytherapy 
  • Requires multiple sessions and high doses of radiation Radiation Emission or propagation of acoustic waves (sound), electromagnetic energy waves (such as light; radio waves; gamma rays; or x-rays), or a stream of subatomic particles (such as electrons; neutrons; protons; or alpha particles). Osteosarcoma 
  • Significant side effects: urethral mucositis Mucositis Stomatitis is a general term referring to inflammation of the mucous membranes of the mouth, which may include sores. Stomatitis can be caused by infections, autoimmune disorders, allergic reactions, or exposure to irritants. The typical presentation may be either solitary or a group of painful oral lesions. Stomatitis, edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema, secondary infection risks

Bulky T2– T4 T4 The major hormone derived from the thyroid gland. Thyroxine is synthesized via the iodination of tyrosines (monoiodotyrosine) and the coupling of iodotyrosines (diiodotyrosine) in the thyroglobulin. Thyroxine is released from thyroglobulin by proteolysis and secreted into the blood. Thyroxine is peripherally deiodinated to form triiodothyronine which exerts a broad spectrum of stimulatory effects on cell metabolism. Thyroid Hormones tumors:

• Limited excisions for distal, smaller T2 tumors 
• Penile amputation Amputation An amputation is the separation of a portion of the limb or the entire limb from the body, along with the bone. Amputations are generally indicated for conditions that compromise the viability of the limb or promote the spread of a local process that could manifest systemically. Amputation: 
  • Determined by extent and location of primary tumor Tumor Inflammation 
  • Partial amputation Amputation An amputation is the separation of a portion of the limb or the entire limb from the body, along with the bone. Amputations are generally indicated for conditions that compromise the viability of the limb or promote the spread of a local process that could manifest systemically. Amputation for distal invasive tumors 
  • Total amputation Amputation An amputation is the separation of a portion of the limb or the entire limb from the body, along with the bone. Amputations are generally indicated for conditions that compromise the viability of the limb or promote the spread of a local process that could manifest systemically. Amputation for extensively invasive tumors
• Chemotherapy Chemotherapy Osteosarcoma ± radiation Radiation Emission or propagation of acoustic waves (sound), electromagnetic energy waves (such as light; radio waves; gamma rays; or x-rays), or a stream of subatomic particles (such as electrons; neutrons; protons; or alpha particles). Osteosarcoma therapy also used to shrink tumor Tumor Inflammation or for large lymph Lymph The interstitial fluid that is in the lymphatic system. Secondary Lymphatic Organs nodes

Lymph Lymph The interstitial fluid that is in the lymphatic system. Secondary Lymphatic Organs nodes:

• Nonpalpable:
  • Low risk (up to T1): surveillance Surveillance Developmental Milestones and Normal Growth for lymph Lymph The interstitial fluid that is in the lymphatic system. Secondary Lymphatic Organs node metastasis Metastasis The transfer of a neoplasm from one organ or part of the body to another remote from the primary site. Grading, Staging, and Metastasis
  • High risk: confirm with node biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma and if positive, proceed with lymphadenectomy
• Palpable lymph Lymph The interstitial fluid that is in the lymphatic system. Secondary Lymphatic Organs nodes: inguinal lymphadenectomy

Differential Diagnosis

• Angiokeratomas: uncommon benign Benign Fibroadenoma, violaceous papules with an overlying scale Scale Dermatologic Examination: Angiokeratomas usually appear on the glans penis Penis The penis is the male organ of copulation and micturition. The organ is composed of a root, body, and glans. The root is attached to the pubic bone by the crura penis. The body consists of the 2 parallel corpora cavernosa and the corpus spongiosum. The glans is ensheathed by the prepuce or foreskin. Penis: Anatomy, but they can also be found on the scrotum Scrotum A cutaneous pouch of skin containing the testicles and spermatic cords. Testicles: Anatomy. In most cases, the lesions are asymptomatic and do not require treatment. 
• Lichen planus Lichen planus Lichen planus (LP) is an idiopathic, cell-mediated inflammatory skin disease. It is characterized by pruritic, flat-topped, papular, purple skin lesions commonly found on the flexural surfaces of the extremities. Other areas affected include genitalia, nails, scalp, and mucous membranes. Lichen Planus ( penis Penis The penis is the male organ of copulation and micturition. The organ is composed of a root, body, and glans. The root is attached to the pubic bone by the crura penis. The body consists of the 2 parallel corpora cavernosa and the corpus spongiosum. The glans is ensheathed by the prepuce or foreskin. Penis: Anatomy): characterized by violaceous papules on the glans: Lichen planus Lichen planus Lichen planus (LP) is an idiopathic, cell-mediated inflammatory skin disease. It is characterized by pruritic, flat-topped, papular, purple skin lesions commonly found on the flexural surfaces of the extremities. Other areas affected include genitalia, nails, scalp, and mucous membranes. Lichen Planus is rarely symptomatic, although some patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship may experience pruritus Pruritus An intense itching sensation that produces the urge to rub or scratch the skin to obtain relief. Atopic Dermatitis (Eczema). Treatment will be for symptomatic control if needed. 
• Condylomata acuminata Condylomata Acuminata Condylomata acuminata are a clinical manifestation of genital HPV infection. Condylomata acuminata are described as raised, pearly, flesh-colored, papular, cauliflower-like lesions seen in the anogenital region that may cause itching, pain, or bleeding. Condylomata Acuminata (Genital Warts): soft papillomatous growths that are highly associated with HPV HPV Human papillomavirus (HPV) is a nonenveloped, circular, double-stranded DNA virus belonging to the Papillomaviridae family. Humans are the only reservoir, and transmission occurs through close skin-to-skin or sexual contact. Human papillomaviruses infect basal epithelial cells and can affect cell-regulatory proteins to result in cell proliferation. Papillomavirus (HPV) infection: Most condylomata acuminata Condylomata Acuminata Condylomata acuminata are a clinical manifestation of genital HPV infection. Condylomata acuminata are described as raised, pearly, flesh-colored, papular, cauliflower-like lesions seen in the anogenital region that may cause itching, pain, or bleeding. Condylomata Acuminata (Genital Warts) are benign Benign Fibroadenoma and associated with low-risk HPV HPV Human papillomavirus (HPV) is a nonenveloped, circular, double-stranded DNA virus belonging to the Papillomaviridae family. Humans are the only reservoir, and transmission occurs through close skin-to-skin or sexual contact. Human papillomaviruses infect basal epithelial cells and can affect cell-regulatory proteins to result in cell proliferation. Papillomavirus (HPV) types 6 and 11. Treatment involves removal of lesions with laser treatment, topical agents, or surgical excision.
• Genital psoriasis Psoriasis Psoriasis is a common T-cell-mediated inflammatory skin condition. The etiology is unknown, but is thought to be due to genetic inheritance and environmental triggers. There are 4 major subtypes, with the most common form being chronic plaque psoriasis. Psoriasis: erythematous plaques with well-defined margins in genital area: These lesions are often asymptomatic but can be pruritic. The presence of other psoriatic plaques on other parts of the body distinguishes this condition from penile cancer.