Determination of Malignancy in Hyperplasias and Extremely Low Grade Neoplasms

Squamous hyperplasias are very common penile lesions that often accompany diverse benign and malignant conditions, sometimes simulating neoplastic processes.35,36 Their morphological aspect is variegated and the surgical pathologist should be aware of their proteiform presentation and learn to separate them from significant neoplastic conditions. Squamous hyperplasias commonly are flat on the surface and on the interface between lesion and stroma, but other variants such as verrucous, papillary, and pseudoepitheliomatous may be found. In general, flat hyperplasia should be distinguished from differentiated PeIN, verrucous hyperplasia from verrucous carcinoma, papillary hyperplasia from papillary NOS carcinoma and pseudoepitheliomatous hyperplasia from pseudohyperplastic carcinomas. In flat hyperplasia there is hyperkeratosis and hypergranulosis, orderly maturation, and absence of cell atypia (Fig. 3.7a). In differentiated PeIN, a closely related lesion, the surface is frequently parakeratotic, there is subtle alteration of the cell maturation process and presence of basal cell atypia, which may be minimal (see Fig. 3.6a). In cases, especially those associated with lichen sclerosus, it may not be possible to

Pseudohyperplastic Carcinomas Penis

Fig. 3.7 (a) Squamous hyperplasia. There is an acanthotic epithelium, hyperkeratosis, and hyper-granulosis but without cytological atypia. (b) Pseudohyperplastic carcinoma can be confused with pseudoepitheliomatous hyperplasia but nests are more irregular and surrounded by an evident stromal reaction, invasion beyond lamina propria is commonly observed, and there is cytological atypia, although minimal

Fig. 3.7 (a) Squamous hyperplasia. There is an acanthotic epithelium, hyperkeratosis, and hyper-granulosis but without cytological atypia. (b) Pseudohyperplastic carcinoma can be confused with pseudoepitheliomatous hyperplasia but nests are more irregular and surrounded by an evident stromal reaction, invasion beyond lamina propria is commonly observed, and there is cytological atypia, although minimal distinguish squamous hyperplasias from differentiated PeIN and immunohisto-chemistry for p53 and Ki-67 may be helpful, as mentioned above.

There are no isolated morphological features to separate verrucous hyperplasia from verrucous carcinoma other than the focality, small size, and often subclinical presentation of verrucous hyperplasias. Morphologically both lesions may be identical and verrucous hyperplasia may indeed represent an early stage of verrucous carcinomas at smaller size. The extreme degree of differentiation characterizes all verrucous hyperplasias and most verrucous carcinomas and atypias can be very subtle in the latter. Clinical background can be helpful in these cases. In papillary hyperplasia the low-power view of the lesion may simulate a papillary carcinoma. However, in the former the papillae lack the complex architecture usually found in the latter. Also, atypical changes are absent in papillary hyperplasia while in papillary carcinomas neoplastic cells show mild to moderate atypia. Finally, papillary hyperplasias tend to remain confined to the lamina propria while most papillary carcinomas invade penile erectile tissues and are associated with a prominent stromal reaction.

Among the most challenging diagnostic problems in the surgical pathology of penile cancer is the distinction of pseudoepitheliomatous hyperplasia from pseudo-hyperplastic carcinomas. On limited biopsy materials these lesions mimic each other and often a wide resection or even circumcision or penectomy specimens are required for correct pathological diagnosis. Deep invaginations of hyperplastic tongues or finger-like prolongations of benign tissues resemble cancer on tangential cuts. Extreme differentiation of invasive pseudohyperplastic carcinomas simulates benign non-neoplastic invaginations. i 7 Epithelial nests are regular and peripheral palisading is a constant feature in pseudoepitheliomatous hyperplasia while in pseudohyperplastic carcinomas epithelial nests are more irregular and peripheral palisading is inconspicuous (Fig. 3.7b). A diagnostic clue in the foreskin, where most of pseudohyperplastic carcinomas occur, is depth of invasion. Hyperplasias

Table 3.2 Differential diagnosis in penile verruciform tumors

Papillary carcinoma, Verrucous

Carcinoma

Giant

Warty carcinoma

NOS

carcinoma

cuniculatum

condylomas

Papillae

Long and spiky,

Variegated

Straight,

Straight,

Arborizing,

prominent

morphology,

prominent

prominent

rounded,

parakeratosis

slight to

hyperkeratosis

hyperkera-

slight

moderate

tosis

hyperkera-

hyperkeratosis

tosis

Fibrovascular

Conspicuous

Irregular and

Very rare or

Very rare or

Conspicuous

cores

variable

absent

absent

Tumor base

Irregular and

Irregular and

Broad and

Broad and

Broad and

jagged

jagged

pushing

pushing

pushing

Histological

Low-grade

Low-grade

Low-grade

Low-grade

Not applicable

grade

heteroge-

heterogeneousa

homogeneous

homoge-

neousa

neous

Koilocytosis

Conspicuous, at

Absent

Absent

Absent

Conspicuous,

surface and

mostly at

deep nests

surface

Metastatic

Low

Low

Nil

Nil

Not applicable

rate

aAreas of high-grade in a minority of cases aAreas of high-grade in a minority of cases are more superficial than cancers and do not affect preputial dartos which is usually invaded by pseudohyperplastic carcinomas. Unlike hyperplasias, invasive carcinoma nests are surrounded by reactive stroma. Intraepithelial squamous pearl formation is more typical of carcinoma and rarely found in hyperplasias. Perineural invasion does not occur in hyperplasia and is occasionally found, although in rare cases, in well-differentiated carcinomas. Several biopsies are sometimes required for a correct classification of hyperplasias or extremely differentiated non-invasive or invasive carcinomas.

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