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Verruca Vulgaris
Human papilloma virus infections probably are universal; those that produce clinical lesions are common. Skin and squamous mucosa are affected. The histologic
changes relate in part to anatomic site and to the numerical type of the virus. Some types are common in association with neoplastic transformations to carcinoma. In this regard, there are relationships between
papilloma virus infections, bowenoid keratinocytic dysplasias, and related invasive carcinomas.
Clinical types include the common verrucae, plantar and palmar variants (including myrmecia), flat warts, and condylomata acuminata. Condyloma acuminatum
preferentially affects squamous mucosa and nearby skin. Flat warts are also common on the squamous mucosae.
Papilloma virus infections produce hyperplasia of the basal unit of squamous epithelium, but the configuration of the lesions probably is more of an expression of a
hyperplasia and hypertrophy of the keratinocytes of the superficial unit of the epithelium. The expanse of the population of keratinocytes is greater along the surface of the affected epithelium than along the
basement membrane zone. This unequal expansion is accommodated by the formation of elongated papillae. In addition, the cells of the superficial unit, including the granular layer, show peri-nuclear vacuolization of
the cytoplasm and nuclear alterations, both of which are distinctive. Affected nuclei are enlarged, show margination of chromatin, and are irregular in outline; the changes qualify as koilocytosis. It should be
emphasized that somewhat similar perinuclear and nuclear changes may be seen in the epidermis in areas showing intra-cellular edema.
In active lesions, particularly those of acral type, some of the nuclei contain homogeneous, pale, acidophilic inclusions; this is particularly true of the
epithelium of myrmecia. Cells of the granular layer show prominent keratohyaline granules and distinctive, crescentric, lavender cytoplasmic inclusions (S11C24P19-1-3). The cytoplasmic inclusions are molded about a centrally placed nucleus.
Koilocytotic changes of viral type are common in the setting of the bowenoid keratinocytic dysplasias. From the opposite perspective, bowenoid changes, that are mild
to moderate, may be overlooked, or may be dismissed as being within the spectrum of koilocytotic changes. In bowenoid processes, nuclear changes are more prominent with variations in nuclear size, loss of nuclear
polarity, hyperchromatism, degeneration and pyknosis of nuclei, and mitotic activity, including atypical forms.
In flat warts (verruca plana), papillomatosis generally is not a prominent feature. Characteristically, the keratin layer is not parakeratotic and is loosely
laminated, but this is a variable quality (S11C24P19-4 & 5). Some “flat” lesions are characterized by cells that have homogeneous,
pale basophilic cytoplasm. This cytoplasmic quality also may be represented in some lesions of epidermodysplasia verruciformis.
In common verrucae, the zones of parakeratosis are most prominent at the tips of the papillae. Inflammation is variable. In some lesions, inflammation is a prominent
feature and may be associated with degenerative changes in the hyperplastic epithelium. The changes, in such lesions, probably are an expression of an immune reaction (a reaction that is comparable to the
destructive changes seen in inflamed lesions of molluscum contagiosum).
The myrmecial form of plantar wart is characterized by a peculiar inversion of the lesion; in addition, viral markers, including intranuclear inclusions, often are
prominent features.
Lesions of condyloma acuminatum tend to be multiple; some are large and solitary. The basic changes are similar to those of the papilloma virus-induced lesions of
the skin, but parakeratosis is a more regular feature. Hypergranulosis and lavender cytoplasmic inclusions tend to be less striking features (S11C24P19-6 & 7). Bowenoid changes are common; if manifested in multiple lesions, bowenoid changes can be characterized as bowenoid
papulosis. Bowen’s disease is a clinical concept embracing the changes of bowenoid keratinocytic dysplasia, bowenoid intra-epithelial carcinoma, and bowenoid (metatypical) carcinoma.
Milker’s Nodule
Milker’s nodule and Orf share features; the causative agents are closely related. The usual source of the disease is infected cows and sheep, respectively.
The epidermis is hyperplastic. In some examples, the papillary dermis is widened and the rete ridges are elongated. Viral inclusions are found in the nuclei and the cytoplasm of some of the infected cells. The
effects of the infection are cytopathic with ballooning degeneration and lysis of cells. The effects are most prominent in the superficial unit of the epidermis (S11C25P20-1-3). Dense lymphoid infiltrates, including plasma cells and histiocytes, are common in the widened
papillary dermis. Transformed (large) lymphoid cells may be prominent in the inflammatory infiltrates in some examples.
Herpes Virus Infections
The virus of herpes simplex and the virus of the varicella-zoster group produce similar lesions; they are members of a sub-group.
Histologically, the lesions of this category of herpes virus infections cannot be distinguished, one from the other. The cytopathic effects of the virus include:
ballooning degeneration, lysis of infected cells, and necrosis, of individual cells, or of broad expanses of infected epithelium. The lesions may be vesicular or ulcerated. Follicles may be involved and, in some
examples, the effects of the infection are most pronounced in follicles. In follicular lesions, the epithelium may undergo extensive lysis leaving behind, in the follicular domain, a defect containing necrotic,
infected, follicular keratinocytes and inflammatory cells.
In most examples, the inflammatory response in the dermis and at the dermal-epidermal interface is composed of lymphocytes and histiocytes. In severe infections
showing areas of necrosis, neutrophils also may be a significant component of the inflammatory reaction.
Inclusions are intranuclear. In formalin-fixed tissue, the inclusion fills the nucleus and pushes chromatin to the periphery of the nucleus (S11C25P20-4 & 5). Other fixatives may produce contraction of the inclusion, resulting in a clear space
between the inclusion and the nuclear membrane (so-called Cowdry type A inclusion). Multinucleated giant keratinocytes, with each nucleus containing an inclusion, also are a feature (S11C30P25-1-3). Inclusions in the nucleus of dying cells are condensed and more acidophilic; they tend to be more easily
recognized (S11C29P24-5-8).
The changes in the epidermis of a lesion of epidermolytic hyperkeratosis may be confused with those of a viral infection (S11C26P21-4 &5).
Molluscum Contagiosum
Molluscum contagiosum is a poxvirus infection. It is a common disease and is a frequent complication in immunosuppressed patients.
The lesions of molluscum contagiosum generally are “inverted.” Columns of squamous cells extend from the epidermis into the adventitial dermis; they are bulbous at
their deep extremities (S11C27P22-1-3). In the hyperplastic epithelium forming the columns hyperplasia of the superficial unit is
greater than that of the basal. Generally, the first histologic evidence of the viral changes can be found near the interface between the superficial and basal units. The initial change is ballooning and pallor of
the cytoplasm of the affected cells (S11C27P22-3). At a slightly more superficial layer, small, uniform vacuoles form in the
cytoplasm and are outlined by lavender, stringy membranes. In the granular layer, near the surface, the cytoplasmic material condenses. It forms a homogeneous, acidophilic body that compresses the nucleus; the
nucleus is displaced eccentrically. The body is delivered with keratinized lamellae into the keratin layer. In the keratin layer, the body becomes basophilic.
Patterns of follicular neogenesis are common at the extremity of the columns in a lesion of molluscum contagiosum; some columns show an immature bulb at its
extremity with bilateral bulges (mantle-like) to each side of the immature bulb. The patterns offer support for the notion that the lesion of molluscum contagiosum has follicular qualities and that the virus induces
follicular neogenesis. In this manner, the inverted pattern is an expression of follicular differentiation (S11C28P23-1-5). In this
same manner, a cystic example is not an epidermoid cyst that has become infected but, rather, is a cystic molluscum contagiosum (S11C27P22-4).
Some examples of molluscum contagiosum are associated with a prominent, delicate, fibrous matrix. Random histologic sections of such a lesion may produce a section lacking the diagnostic nests of keratinocytes; such
a section may show only the loose, delicate fibrous matrix. Requests for additional sections will usually produce patterns that are more representative of the nature of the lesion.
Some lesions are inflamed; these are lesions that are in the process of “spontaneously regressing.” The regression is mediated at the level of an inflammatory
reaction that is lymphohistiocytic in character. The infiltrates of inflammatory cells are supported by a delicate fibrous matrix. Some of the nests of degenerating keratinocytes are sloughed along the surface;
islands of inflamed, necrotic epithelium become separated from the neighboring tissue. Some of the nests of viable epithelium show erosions along their interface with the inflammatory infiltrate (S11C27P22-5).
Schwartz JL, Myskowski PL: Molluscum contagiosum in patients with human immunodeficiency virus infection. J Am Acad Dermatol 1992;27: 583-8.
Buntin DM, et al: Sexually transmitted diseases: viruses and ectoparasites. J Am Acad Dermatol 1991;25: 527-34.
Vibrio Vulnificus
Vibrio vulnificus is associated with bullous, or necrotic lesions of the extremities; the cutaneous lesions are the result of a septicemia. This disease is
encountered in individuals with lowered immunity; patients with chronic liver disease are at risk.
The skin lesions are associated with a vasculitis. The vessels show necrosis and thrombosis. The affected tissues shows necrosis and extravasation of red blood cells (S11C29P24-1-4).
Varicella
Varicella is a herpes virus infection. The histologic features are similar to those seen in herpes simplex (S11C29P24-5-8, & S11C30P25-1-3).
Hand-Foot-Mouth Disease
Hand-foot-mouth disease is a benign viral exanthem of childhood. The histologic changes are not well documented (S11C30P25-4-6, & S11C31P26-1-3).
Diven DG: An overview of poxviruses. J Am Acad Dermatol 2001;44:1-14.
Hulsebosch HJ, et al: Human immunodeficiency virus exanthem. J Am Acad Dermatol 1990;23: 483-6.
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