Penis and Scrotum
Peter A. Humphrey
I. NORMAL ANATOMY. The penis is anatomically composed of three parts: posterior (root); central body or shaft; and anterior portion composed of glans, coronal sulcus, and foreskin (prepuce). In the shaft there are three cylinders of erectile tissues: a ventral corpus spongiosum surrounding the urethra and two corpora cavernosa. Histologically, the erectile tissues are characterized by numerous vascular spaces with surrounding smooth muscle fibers (e-Fig. 30.1).* The tunica albuginea, a sheath of hyalinized collagen, encases the corpora cavernosa. All three corpora are surrounded by Buck’s fascia, adipose tissue, dartos muscle, dermis, and a thin epidermis. Distally, the corpus spongiosum forms the conical glans, which is also composed of a stratified squamous epithelium, lamina propria, tunica albuginea, and corpora cavernosa. The coronal sulcus is a cul-de-sac just below the glans corona. The foreskin is a double membrane that has five layers: mucosal epithelium similar to glans epithelium, lamina propria, dartos smooth muscle, dermis, and epidermis.
The scrotum contains the testes and lower spermatic cords. It consists of skin that covers the dartos smooth muscle, fibers of the cremasteric muscle, and several layers of fascia. The skin is pigmented, hair bearing, and loose, with numerous sebaceous and sweat glands. Lymphatic drainage is to the superficial inguinal lymph nodes.
II. GROSS EXAMINATION AND TISSUE SAMPLING. Tissue samples include mucosal or skin biopsies, penile urethral biopsies, foreskin resection specimens, and partial and total penectomy specimens.
A. Punch and shave biopsies of penile glans and skin should be handled as skin biopsies from other sites (see Chap. 38).
B. Foreskin resection is indicated for primary carcinomas of this site. The entire periphery of the mucosal margin should be submitted as a shave resection margin (usually in three to four sections). The foreskin should then be pinned and fixed overnight in 10% formalin. Several full-thickness sections should be examined microscopically to permit evaluation of all five layers.
C. For partial penectomy specimens, the surgical division of the penis is made 2 cm proximal to gross tumor extent. Three to four frozen sections are typically necessary to sample the cut surface of this margin. Permanent sections are taken as described below.
D. For total penectomy specimens, only proximal urethral and periurethral margin tissues should be submitted for frozen section, unless the mass is grossly close to or involves the skin, which should also then be sampled. For permanent sections of both partial and total penectomy specimens, the foreskin (when present) should be removed and handled as noted previously. A thin 2-mm shave of all the structures of the shaft margin should be taken, if not already sampled by frozen section. One to three additional transverse sections should be taken from the glans. Any mass(es) should be sampled to demonstrate pattern of growth, depth of extension, and relationship to normal anatomic structures.
E. Lymph nodes. There may be a clinical request for frozen section(s) of enlarged inguinal lymph nodes; if positive for carcinoma, a more extended ilioinguinal
lymph node dissection may follow. Bilateral inguinal lymphadenectomy specimens may also be received after removal of the primary tumor and a course of antibiotics, or in patients with T2 tumors, high-grade tumors, or tumors with vascular invasion (Crit Rev Oncol Hematol. 2005;53:165).
A nomogram has been developed to predict nodal metastases using the presence of clinically palpable groin lymph nodes and histologic lymphovascular invasion in the primary tumor (J Urol. 2006;175:1700). The utility of sentinel lymph node sampling is not yet settled. A prognostic index has also been generated to predict nodal metastasis (Am J Surg Pathol. 2009;33:1049); this index incorporates histologic grade, deepest anatomic level involved by cancer, and the presence of perineural invasion by carcinoma.
III. DIAGNOSTIC FEATURES OF COMMON DISEASES OF THE PENIS AND SCROTUM
A. Inflammation and infection. Three categories can be defined: inflammatory conditions specific to penis and scrotum, systematic dermatoses (discussed in Chap. 38), and sexually transmitted diseases (BJU Int. 2002;90:498).
1. Phimosis, the clinical condition in which the foreskin cannot be retracted behind the glans penis, is associated with fibrosis, inflammation, and edema of the prepuce.
2. Paraphimosis is diagnosed clinically when the foreskin cannot be advanced back over the glans secondary to fibrosis and inflammation.
3. Balanoposthitis is an inflammation of the glans penis and prepuce, usually in uncircumcised men with poor hygiene.
4. Balanitis, or inflammation of the glans, occurs in several forms.
a. Plasma cell balanitis (Zoon balanitis) can clinically and grossly mimic carcinoma in situ, with presentation as brown or red patches or plaques. The histologic appearance can vary with time, and the inflammatory cell infiltrate can vary from patchy and lymphoplasmacytic (early) to dense and plasmacytic (later) (Am J Dermatopathol. 2002;24:459).
b. Balanitis xerotica obliterans (BXO) is lichen sclerosus of the glans and prepuce that macroscopically appears as a white patch or plaque. Histologically, the squamous epithelium is typically atrophic and hyperkeratotic, with a band of pale homogenous collagen in the upper dermis and an underlying lymphocytic infiltrate (e-Fig. 30.2). Complications include meatal stenosis (urethral stricture), and very uncommonly, squamous cell carcinoma.
c. Balanitis circinata microscopically resembles pustular psoriasis and is seen in Reiter syndrome, which includes nongonococcal urethritis, conjunctivitis, and arthritis.
5. Human papillomavirus (HPV) infection can lead to condyloma acuminata. The growth is typically papillary or warty, and histologically papillomatosis, acanthosis, parakeratosis, and hyperkeratosis are found; intraepithelial neoplasia may also be present. Koilocytes with wrinkled nuclear membranes, nucleomegaly, cytoplasmic halos, and binucleation may be prominent or inconspicuous. The causal HPV serotypes are usually 6 or 11, but it is not necessary to verify the presence of HPV. Bowenoid papulosis is also an HPV-related proliferation that presents with multiple 2 to 10 mm papules than can coalesce to form plaques; it is usually caused by serotypes 16, 18, and/or 35. Microscopically, although the appearance is similar to carcinoma in situ, the clinical course is typically self-limited and benign.
6. Herpes simplex virus (HSV) infection of the male genitalia is usually caused by subtype 2, which produces multiple vesicles. The diagnosis may be confirmed by scraping and performance of a Tzanck smear, which reveals multinucleated giant cells with intranuclear inclusions.
7. Scabies is an infestation by a mite that burrows into the keratin layer of the epidermis with generation of erythematous papules and nodules. Detection
of the mites may be accomplished via scrapes or biopsy. In tissue sections, the 400 µm mite, eggs, or egg walls, are diagnostic. Dermal eosinophils and epidermal spongiosis are characteristic responses.
8. Pediculosis pubis is an infection by Pediculus pubis, also known as the crab louse. Biopsy is not necessary; the lice may be seen by a magnifying lens.
9. Syphilis is caused by Treponema pallidum, a gram-negative spirochete. The primary lesion, the chancre, is a single, round, craterlike painless ulcer most often located on the glans or prepuce. Biopsy is not usually necessary, but if done (e.g., when syphilis is not clinically suspected) it shows a perivascular lymphoplasmacytic infiltrate. The spirochetes may be identified in the epidermis or in dermal perivascular regions by silver stains (Steiner, Dieterle, or Warthin-Starry). The secondary and tertiary stages of syphilis are characterized by condyloma latum and gumma, respectively. Smears from the gray maculopapules of condyloma latum should be examined by dark-field microscopy for spirochetes since biopsy may yield nonspecific findings. The gumma is a necrotic mass with surrounding granulomatous inflammation, and associated obliterative endarteritis with perivascular plasma cells.
10. Gonorrhea is caused by Neisseria gonorrhoeae, a gram-negative diplococcus. Urethritis with urethral discharge may lead to urethral stricture. Biopsies are hardly ever performed.
11. Lymphogranuloma venereum is due to Chlamydia trachomatis. Vesicles, then ulcers, develop in the primary genital phase; biopsies are not useful for diagnosis of the primary phase. In the secondary stage, patients develop painful inguinal lymphadenopathy (bubo). Histologically, the lymph nodes demonstrate stellate necrosis surrounded by palisaded histiocytes, a nonspecific picture that can also be seen in cat scratch fever, tularemia, bubonic plague, and fungal and atypical mycobacterial infections.
12. Granuloma inguinale is caused by Calymmatobacterium granulomatis, a gram-negative intracellular bacillus. Infection results in ulcers. Smears or biopsy sections reveal histiocytes with inclusions (Donovan bodies), best visualized by Warthin-Starry or Giemsa stains.
13. Chancroid is caused by Haemophilus ducreyi, a gram-negative rod, and is typified by painful nonindurated penile ulcers and lymphadenopathy. The organisms can be found in smears or histologic sections stained with Giemsa, Gram, or methylene blue stains.
14. Molluscum contagiosum is caused by a DNA poxvirus and produces multiple small dome-shaped papules with a central umbilication. Biopsy sections show a crater with an acanthotic epidermis and the diagnostic intracytoplasmic viral inclusions (molluscum bodies).
15. Penile infections in acquired immunodeficiency syndrome (AIDS) include almost all sexually transmitted infections including gonorrhea, syphilis, herpes, candidiasis, chancroid, molluscum contagiosum, HPV, scabies, and Reiter syndrome.
16. Lipogranulomas in the scrotum or penis are secondary to injections of oil-based chemicals. Sections show a foreign body, lymphoplasmacytic, and histiocytic reaction to lipid droplets that appear as cleared spaces.
17. Hidradenitis suppurativa, more typical of the sweat glands in the axilla, can also involve the scrotum. Acute and chronic inflammation, fibrosis, and even sinus tract formation can occur.
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