Penile Intraepithelial Neoplasia

Penile intraepithelial neoplasia is classified into four categories depending on the degree and type of cell differentiation: differentiated ("simplex"), basaloid, warty, and warty-basaloid. Regardless of its histological aspect PeIN clinically presents as whitish irregular areas, sometimes with a pearly aspect, either as an isolated lesion or in continuity or adjacent to an invasive tumor. Occasionally, foci of PeIN are found as multicentric lesions, separated from the main invasive component. Differentiated PeIN is characterized by acanthosis, parakeratosis, and atypical epithelial cells with retained tendency to squamous maturation. In its classical form nuclear atypia, consisting of nuclear pleomorphism, hyperchromasia, irregular nuclear membrane, coarse chromatin, and evident nucleolus, is more prominent at the bottom layers (Fig. 3.6a). At both ends of the spectrum there are minimally atypical differentiated PeIN, which can be difficult to differentiate from squamous hyperplasia, and pleomorphic differentiated PeIN, which can be confused with basaloid or warty PeIN. In minimally atypical differentiated PeIN there are p53/ Ki-67 positive cells above the basal layer. In pleomorphic PeIN the most distinguishing feature is the presence of ample and eosinophilic (keratinized) cytoplasm and a greater degree of nuclear pleomorphism, features contrasting to those found in basaloid PeIN (see below). In addition, koilocytes are absent in differentiated PeIN and are conspicuous in warty PeIN.

In basaloid PeIN the entire epithelium is replaced by a monotonous population of small to intermediate-sized cells with scant basophilic cytoplasm, indistinctive cell borders, abundant apoptosis, and high mitotic rates (Fig. 3.6b). Occasionally there are larger basophilic and/or spindle cells. The surface and base are usually flat and a parakeratotic layer may be present. In warty PeIN, epithelial cells are more pleomorphic, cytoplasm is ampler, and koilocytes are easily found, mainly in the superficial layers (Fig. 3.6c). Caution should be taken to not confuse epithelial clear cells with koilocytic changes. Neoplastic cells with clear and ample cytoplasm can be observed in differentiated PeIN, especially in the uppermost layers. Koilocytes should exhibit wrinkled and hyperchromatic nuclei with a well-defined perinuclear halo. Binucleation and even multinucleation are common findings and pleomorphic

Fig. 3.6 Precancerous lesions. (a) Differentiated PeIN showing atypical cells distributed throughout the entire epithelium (although more prominent at bottom layers), suprabasal acantholysis, retained squamous maturation, and parakeratosis. (b) In basaloid PeIN the epithelium is replaced by a monotonous proliferation of small to intermediate-sized cells with scant cytoplasm, indistinctive cellular borders, and high mitotic/apoptotic rate. (c) Warty PeIN is characterized by a spiky parakeratotic surface and conspicuous koilocytosis, more evident at upper layers. (d) Lichen scle-rosus, recognized by the dense subepithelial collagenization in the lower left field, associated with differentiated PeIN ("atypical lichen sclerosus")

Fig. 3.6 Precancerous lesions. (a) Differentiated PeIN showing atypical cells distributed throughout the entire epithelium (although more prominent at bottom layers), suprabasal acantholysis, retained squamous maturation, and parakeratosis. (b) In basaloid PeIN the epithelium is replaced by a monotonous proliferation of small to intermediate-sized cells with scant cytoplasm, indistinctive cellular borders, and high mitotic/apoptotic rate. (c) Warty PeIN is characterized by a spiky parakeratotic surface and conspicuous koilocytosis, more evident at upper layers. (d) Lichen scle-rosus, recognized by the dense subepithelial collagenization in the lower left field, associated with differentiated PeIN ("atypical lichen sclerosus")

koilocytes, in which the nuclear pleomorphism is greater, can also be observed. In warty PeIN the surface is spiky and parakeratosis is invariably found. The presence of a more pleomorphic cell population, koilocytes, and a spiky surface allows the distinction from basaloid PeIN. Finally, in warty-basaloid PeIN both aforementioned patterns coexist, usually with the basaloid component at the bottom layers and the warty areas at the surface. In rare occasions a mixed differentiated and warty/basaloid pattern is observed in the same specimen but usually separated one from another as multicentric lesions.

Over expression of p165 NK4a can help in distinguishing differentiated PeIN from in situ lesions depicting warty and/or basaloid features.37 The former is usually negative while the latter tends to be positive, especially with basaloid and warty-basaloid PeIN. There is a striking correspondence between the type of PeIN and the subtype of associated SCC.37 Differentiated PeIN tends to be found in association with keratinizing variants of penile SCC such as usual, papillary, and verrucous carcinomas while warty and/or basaloid PeIN are commonly found in tumors with similar invasive morphology. Mixed tumors also tend to present PeIN with mixed features.

How To Reduce Acne Scarring

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Acne is a name that is famous in its own right, but for all of the wrong reasons. Most teenagers know, and dread, the very word, as it so prevalently wrecks havoc on their faces throughout their adolescent years.

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