reveals, from outside to inside, the skin, dartos, penile fascia (Buck fascia), albuginea, erectile tissue (corpus spongiosum and corpora cavernosa), and urethra (Fig. 14-4).3 The penile or pendulous urethra is ventrally located in the corpus and head and runs surrounded by the corpus spongiosum (Fig. 14-4).
network of trabecula (Fig. 14-7). The vascular structures of the corpora cavernosa are thicker and more complex, and the connective tissue of the trabecula contains more smooth muscle bundles when compared with the corpus spongiosum.3 There are also thin nutritional vessels within the matrix of the corpora cavernosa. The tunica albuginea is a hyaline fibrous sheath measuring approximately 1 to 3 mm in thickness that surrounds and separates the corpus spongiosum and corpora cavernosa (Figs. 14-4, 14-6C, and 14-7). The Buck fascia surrounds the tunica albuginea and erectile tissues of the shaft and extends distally to the coronal sulcus where it is continuous imperceptibly with the connective tissue of the dartos or with the lamina propria (Figs. 14-4 and 14-6C). The Buck fascia is an important pathway of tumor progression and is composed of loose fibroadipose tissue with numerous blood vessels and nerves (Fig. 14-6C). It is surrounded by the dartos of the shaft that is present underneath the skin surface (Fig. 14-4).
FIGURE 14-4 ▪ Diagram of a cross section passing through the mid shaft of a partial penectomy specimen. S, skin; D, dartos; BF, Buck fascia; A, tunica albuginea; CC, corpus cavernosum; CS, corpus spongiosum; U, urethra.
are present in the superficial lamina propria just underneath the epithelium.6 The dartos is a muscular layer, in which irregularly arranged bundles of smooth muscle are seen in a background of loose connective tissue associated with vascular structures, nerves, and pacinian corpuscles.3 The skin is composed of the epidermis with a slightly hyperpigmented basal layer and a few small adnexal structures in the dermis.
FIGURE 14-9 ▪ Histologic features of the penile urethral epithelium composed of stratified basaloid cells with a columnar cell layer at the surface.
vein runs along the superficial dorsal vein but in a deeper plane beneath the Buck fascia. It receives the blood from the glans and corpora cavernosa and courses backward in the middle line between the dorsal arteries. The deep dorsal vein divides into two branches that drain into the pudendal plexus. It is noteworthy that the cavernous venous system delays venous drainage and in doing so assists in maintaining erections.14 The deep dorsal vein of the penis has a connection with the vertebral veins; hence it is possible for metastases to make their way to the vertebrae or even to the skull and brain without going through the heart and lungs. Pyogenic organisms may be transported by the same route.2
the penis to the meatus. The embryologic abnormality often is an isolated skin and dartos defect. Penile torsion may also be associated with hypospadias or hooded prepuce.17,18
opens on the glans (first degree hypospadias) in about 50% to 75% of cases. Second degree (when the urethra opens on the shaft) (Fig. 14-10B) and third degree (when the urethra opens on the perineum) occur in up to 20% and 30% of cases, respectively (Box 14-1). The more severe degrees are more likely to be associated with other malformations. Hypospadias is among the most common birth defects of the male genitalia.17,18
usually starts as a painless papule that enlarges and ulcerates centrally. This ulcerated lesion that has an indurated base is known as the hard chancre. Chancres are most often solitary and in the penis commonly affect the inner prepuce, coronal sulcus, penile shaft, and penile base.21 Secondary syphilis results from hematogenous dissemination of organisms. Condyloma lata, the characteristic anogenital lesions of secondary syphilis, are large verruciform papules, nodules, or plaques, which may become confluent.35 Gummas are characteristic of tertiary syphilis. Histologic hallmark of the lesions is obliterative endarteritis surrounded by a plasma cell-rich infiltrate (Fig. 14-11A and B). In primary syphilis the endarteritis can be found at the base of the ulcer. Secondary syphilis is usually associated with psoriasiform epidermal hyperplasia with a superficial lichenoid and deep perivascular plasma cell-rich infiltrate; the endarteritis can be superficial or deep.36, 37, 38 Spongiform pustular lesions can also be seen. The causative agent can be identified in primary and secondary lesions using Steiner or Warthin-Starry stains (Fig. 14-11C). The presence of T. pallidum in the tissues can also be detected by immunohistochemistry and by PCR. Condyloma latum is usually characterized by prominent epidermal hyperplasia and numerous neutrophils in the epidermis and cornified layer.36, 37, 38 When intraepidermal/intracorneal neutrophils are prominent, spirochetes tend to be easily identified within the epidermis (Fig. 14-11C). Gummas of tertiary syphilis are necrotizing granulomatous lesions associated with obliterative endarteritis. Treponema organisms usually cannot be demonstrated in these lesions by special stains. Reactivation of syphilis in patients infected with human immunodeficiency virus (HIV) is becoming more frequent39,40 and the affected patients may present with an atypical course.
ulcer with tender adenopathy is suggestive of chancroid. Phagedenic chancroids are widely necrotic and destructive lesions usually secondary to superimposed infection by Fusobacterium organisms. Histologically, the soft chancre is characterized by a zonation phenomenon. The upper layer shows necrosis, fibrin, and numerous neutrophils; the middle layer shows abundant granulation tissue with prominent blood vessels, some with partial thrombosis; the deepest layer shows an intense plasma and lymphoid cell infiltrate.37,38,42 Diagnosis is made isolating H. ducreyi on special culture media.
and a nonspecific granulation tissue with plasma cells and lymphocytes. Nonnecrotizing granulomas composed of epithelioid histiocytes and a few giant cells surrounded by plasma cells also can be seen.37,44 The lymph nodes show focal aggregates of neutrophils in necrotic foci followed by follicular hyperplasia with massive plasma cell infiltration. The small suppurative foci eventually coalesce to form the classical stellate abscesses with surrounding epithelioid cells and multinucleated giant cells.45 Sinuses and tracts can develop. Old lesions are characterized by extensively fibrotic lymph nodes. The microorganisms cannot be seen by ordinary histologic stains. The diagnosis can be confirmed by cultures. Serology may be useful.44
that can look like fibroepithelial papillomas. Less frequently, condylomata may closely resemble seborrheic keratoses with basaloid cells, horn pseudocysts, and inconspicuous viral cytopathic changes (Fig. 14-14). Flat condylomata may also be seen (Fig. 14-15). Condyloma acuminatum is a benign lesion showing normal maturation with no atypias except for the koilocytosis that is usually restricted to the upper levels of the epithelium. Interestingly, it has been demonstrated that in genital locations lesions with features of fibroepithelial polyps and seborrheic keratosis without koilocytosis are often associated with HPV.57,58 Methods of virus identification include immunohistochemistry, in situ hybridization, and polymerase chain reaction.55,56,59,60
FIGURE 14-14 ▪ Old lesion of condyoma acuminatum mimicking a seborrheic keratosis. The koilocytic changes are more difficult to detect in such old lesions.
selectively within those cells.21,37,38 The result of T helper cell depletion is a severe defect in cell-mediated immunity making the affected individuals particularly susceptible to infections. AIDS patients are often concomitantly infected with several different types of microorganisms. Skin diseases (including genital lesions) are common manifestations of HIV infection and they can be classified as noninfective dermatosis, infective disorders, and neoplasms.38,64, 65, 66, 67 These conditions are discussed in other parts of this chapter; however, they can be more frequent or severe in patients with AIDS. Immunosuppression often results in an atypical presentation, increased severity, and aggressive course of a dermatosis. Such lesions may also fail to respond to standard treatment regimens. A high index of suspicion is important to make the diagnosis.
FIGURE 14-17 ▪ Molluscum contagiosum. There are endophytic lobules of squamous epithelium separated by compressed dermis. Infected keratinocytes show the characteristic intracytoplasmic Henderson bodies.
also transfer the fungus from the feet or other areas by hand. Clinically, the lesion presents as an erythematous, often annular plaque with scaling. Histologically, the fungus may be difficult to identify on H&E-stained sections. Superficial fungal infections should be especially suspected when neutrophils are present in the squamous epithelium and keratin (often parakeratotic) layer. Special stains such as diastase-PAS and silver stains will highlight the presence of septate hyphae, frequently admixed with globose hyphal segments and chains of arthroconidia within the stratum corneum.22,37,38
histologic examination, there is usually a dermal lymphoid infiltrate with variable numbers of eosinophils. Several serial sections may need to be examined before identifying the burrow (which is almost entirely located within the cornified layer) and its contents (e.g., mite, eggs or fecal deposits).
thinning of the suprapapillary plates. The papillary dermis appears edematous with prominent blood vessels.37,38 There is confluent parakeratosis containing neutrophilic aggregates and diminution to loss of granular layer (Fig. 14-21). Lesions in the genital location, however, may show more prominent spongiosis and even erosion. Therefore, often, the histologic features are not typical and the diagnosis is supported by the presence of classical psoriasis at other sites (scalp, nails, extensor surface, etc.). When dealing with a psoriasiform dermatitis containing neutrophils in the parakeratotic layer, a PAS stain to rule out superficial fungal infection is mandatory.
was described in the penis as balanitis xerotica obliterans by Stuhmer in 1928; however, because some authors prefer to use the term balanitis xerotica obliterans for the end-stage condition and to unify gynecologic and urologic terminology, the use of lichen sclerosus is recommended.75,76 Penile lichen sclerosus tends to affect middle-aged adults. Grossly, the lesions appear as white gray, irregular geographic and atrophic areas most commonly compromising the inner aspect of the foreskin, glans, and perimeatal region. Erosion, ulceration, and elevated hyperkeratotic foci may also be seen. In advanced cases, the preputial mucosal folds may disappear resulting in acquired phimosis or paraphimosis.21 Histologically, the lesions are characterized by an atrophic epithelium frequently intermixed with hyperplastic areas, vacuolar alteration of the basal layer, and a thickened lamina propria with the classical hyalinization/sclerosis (Fig. 14-23A).37,38 A variable amount of band-like lymphoid infiltrate is usually seen underneath the area of hyalinization. Because of marked basal cell vacuolar alteration, some cases may show dermal-epidermal clefting. Marked edema of the lamina propria may precede or coexist with the classical sclerotic changes.37,38 Lichen sclerosus is a superficial mucosal disorder preferentially affecting the epithelium and lamina propria and typically sparing the preputial dartos and corpus spongiosum of the glans. The lesions, however, tend to be broad and multifocal and may affect more than one epithelial compartment, and even extend to the epithelium and lamina propria of the distal urethra.76 While extragenital lichen sclerosus appears to carry no risk for malignant transformation, the relationship of anogenital lichen sclerosus and squamous cell carcinoma is well-documented.76, 77, 78, 79, 80, 81, 82 In a prospective study, the incidence of carcinoma arising in the setting of long-standing lichen sclerosus of the penis was 9.3%.80,81 In a retrospective review of 200 penectomy specimens with penile invasive carcinoma, 33% of the cases were associated with lichen sclerosus76 and this figure was much higher (69%) when considering carcinomas affecting the foreskin exclusively.82 When present adjacent to invasive carcinomas, lichen sclerosus is almost always associated with areas of epithelial hyperplasia and frequently shows squamous cell atypias (Fig. 14-23B).76,82 A significant association of lichen sclerosus with special (usually HPV-unrelated) variants of carcinoma such as usual, pseudohyperplastic, verrucous, and papillary carcinoma has been demonstrated. There is also a distinct association of lichen sclerosus with differentiated (simplex) PeIN.83 These findings suggest that lichen sclerosus may represent a precancerous condition for a subset of penile squamous cell carcinoma, especially the HPV-unrelated variants.
before making this diagnosis. Based on the nonspecific findings in Zoon balanitis and the similarities with other plasma cell-rich dermatitis and mucositis, the more generic term idiopathic lymphoplasmacellular mucositis-dermatitis was suggested by some authors to encompass etiologically uncertain lymphoplasmacellular infiltrates in the skin and mucosal surfaces.86
phimosis.38,87 Histologically, there is a subepithelial blister associated with a mixed inflammatory infiltrate containing lymphoid cells, eosinophils, neutrophils, and plasma cells. The lamina propria may be edematous or fibrotic. Apart from scarring fibrosis in old lesions, these changes are identical to those seen in bullous pemphigoid. The mucosal lesions are often eroded and ulcerated showing fibrosing-granulation tissue with no specific acute and chronic inflammation. Direct immunofluorescence findings on perilesional mucosa (the site of choice) are similar to those seen in bullous pemphigoid.
the one seen in the scrotum is produced (Fig. 14-74).95 This reaction may occur several years after the injection.96
there is subtle but abnormal maturation in all levels of the epithelium. Despite the subtle changes, we believe that differentiated PeIN represents a high-grade (although differentiated) lesion that may evolve to frank invasive carcinoma without showing more significant atypia (Fig. 14-30).83,118,119,121
FIGURE 14-30 ▪ Differentiated PeIN (left) is seen adjacent to a well-differentiated invasive carcinoma (right).
benign condyloma, with the latter not being considered a preneoplastic condition. p16 is usually overexpressed in undifferentiated PeIN (Fig. 14-34) and negative in differentiated PeIN, further supporting the association of undifferentiated PeIN with high-risk variants of HPV.112 Other rare morphologic patterns of precursor lesions include pleomorphic, pagetoid, clear, spindle, and small cell; all of these are more likely to represent variants of the HPV-related group. A recent study found a distinctive geographical distribution of penile precursor lesions. PeIN with warty and/or basaloid features predominated in low-incidence areas, whereas differentiated PeIN was more prevalent in endemic regions for penile cancer. With few exceptions there is a good correlation between the microscopic appearance of the preinvasive process and the associated invasive carcinoma, further supporting the concept of a dual pathway of penile tumorigenesis.
FIGURE 14-31 ▪ Undifferentiated PeIN, basaloid type. There is replacement of the epithelium by a monotonous proliferation of small round cells with high nuclear/cytoplasmic ratio.