Who Update Penis

Department of Pathology
IRCCS National Cancer Institute Milan
Penile tumors
WHO update
MAURIZIO COLECCHIA
MILAN
WHO 2016 Pathological classification of Department of Pathology
penile intraepithelial neoplasia (PeIN)
Non–HPV-related PeIN
Differentiated (simplex) PeIN
HPV-related PeIN
Basaloid PeIN
Warty PeIN
Warty–basaloid PeIN
Other rare patterns of PeIN

Localization
Differentiated PeIN commonly affects the foreskin, and
undifferentiated PeIN tends to affect the glans.
However, both types may affect any penile anatomical
compartment.
Differentiated PeIN
• Differentiated (simplex) PeIN is characterized

by a thickened epithelium, usually associated
with elongated and anastomosing rete ridges,
subtle abnormal, whorling and keratin pearl
formation (usually in deep rete ridges),
spongiosis and sometimes acantholysis, and
atypical basal layer cells (with nuclear
enlargement, hyperchromatic nuclei, and
prominent nucleoli).
• Parakeratosis is common.
DIFFERENTIATED PEIN
At low power, the atypia seems to be present only in

lower levels of the epidermis; however, at higher power,
it is clearer that there is subtle but abnormal maturation in
all levels of the epithelium in the majority of cases. There
is a spectrum ranging from mostly basal cell atypia (in
few cases), to obvious atypias in about a third to two
thirds of the epithelial thickness (in the majority of cases)
and (rarely) pleomorphic features.
It is optional to grade differentiated PeIN

in low- and high-grade categories.
differentiated PeIN
may be difficult to distinguish
from reactive conditions such as
squamous hyperplasia,
pseudoepitheliomatous hyperplasia
lichen simplex chronicus
”hyperplastic lichen”
High grade squamous
intraepithelial lesion
•Marked atypia throughout the entire epithelium

•The cells are large and pleomorphic , marked inflammatory infiltration
•Atypical mitoses
Undifferentiated PeIN Department of Pathology
basaloid type
Acanthotic thickening of the epithelium, which shows partial

replacement by small basaloid atypical cells.
basaloid PeIN Department of Pathology
• replacement of the squamous epithelium by small

basaloid (round or oval) atypical cells
• mitoses are frequent

•
• it is similar to vulvar or cervical analoguous lesions
• it occurs in >50% of basaloid invasive carcinoma
• HPV-related
Undifferentiated PeIN Department of Pathology
warty type IRCCS National Cancer Institute Milan

Warty intraepithelial lesion
• Flat or exophytic papillary lesions
• Hyperkeratosis, parakeratosis,marked nuclear

pleomorphysm, koilocytosis, atypical mitoses
• HPV-related
• Mixed with basaloid type PeIN

Warty–basaloid penile intraepithelial neoplasia
In this variant, there is a variable mixture of warty and
basaloid cells. These mixed lesions tend to have a
spiking surface with koilocytic changes, whereas the
lower half of the epithelium is predominantly composed
of small basaloid cells.

Warty basaloid neoplasia
• Shares with warty SCC a higher association with

HPV infection
• Probable common pathogenesis:
• Warty – basaloid SCC is a recognized entity (>10%

of basaloid cells) with intermediate features (grade,
nodal mets, survival), similar to usual P-SCC
Chaux et al Mod Pathol 23:896–904;2010

• Penile intraepithelial neoplasia (PeIN) is an

alteration of the penile squamous epithelium
characterized by dysplastic changes. PeIN is a
putative precursor of invasive squamous cell
carcinoma.
• HPV related and HPV unrelated lesions have

distinctive morphological expressions , the former
predominantly composed of small basaloid cells
with more or less prominent koilocytic changes
and the latter composed of keratinizing squamous
cells (differentiated)
From the pathogenic point of view, penile cancers may be grouped in

human papillomavirus-related and unrelated tumors, each one of them with
distinctive morphologic features. The former are predominantly composed
of small, undifferentiated basaloid cells, with more or less prominent
koilocytic changes, and the latter of keratinizing differentiated squamous
cells. The same cellular types are observed in precancerous lesions. On the
basis of these observations, we constructed a novel nomenclature for penile
precancerous lesions and classified them as penile intraepithelial neoplasia
(PeIN) of differentiated, warty, basaloid, and warty-basaloid types
p16INK4a Department of Pathology
WARTY CARCINOMA Department of Pathology
WARTY CARCINOMA Department of Pathology
Mean age 51 years

Unicentric
Multiple anatomical compartments involved
HPV+ 22-100% ( HPV 6/16)
Mean size 5 cm
BASALOID CARCINOMA Department of Pathology
• 4%-10% of penile SCC

• Solid tumor, deeply invasive into the corpus
• spongiosum or cavernosum
• HPV 70-80%
• Recurrence 30%; nodal mets 50-100%
• High mortality (up to 25%)
Chaux et al J.Urology 2010

Basaloid penile SCC Department of Pathology
Warty-Basaloid penile SCC Department of Pathology
• Shares with warty SCC a higher association with

HPV infection
• Probable common pathogenesis:
• Warty – basaloid SCC is a recognized entity (>10%

of basaloid cells) with intermediate features (grade,
nodal mets, survival), similar to usual P-SCC
Chaux et al Mod Pathol 23:896–904;2010

PAPILLARY CARCINOMA Department of Pathology
Courtesy
A Cubilla
PAPILLARY CARCINOMA Department of Pathology
VERRUCOUS CARCINOMA Department of Pathology
PSEUDOGLANDULAR Department of Pathology
CARCINOMA
PSEUDOGLANDULAR Department of Pathology
CARCINOMA
“Adenoid pattern” Department of Pathology
SARCOMATOID CARCINOMA Department of Pathology
MIXED CARCINOMA
PSEUDOHYPERPLASTIC Department of Pathology
CARCINOMA

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Department of Pathology

IRCCS National Cancer Institute Milan

penile intraepithelial neoplasia (PeIN)

Differentiated (simplex) PeIN

Other rare patterns of PeIN

Differentiated PeIN commonly affects the foreskin, and

undifferentiated PeIN tends to affect the glans.

However, both types may affect any penile anatomical

• Differentiated (simplex) PeIN is characterized

At low power, the atypia seems to be present only in

It is optional to grade differentiated PeIN

•Marked atypia throughout the entire epithelium

Acanthotic thickening of the epithelium, which shows partial

• replacement of the squamous epithelium by small

• mitoses are frequent

• it occurs in >50% of basaloid invasive carcinoma

warty type IRCCS National Cancer Institute Milan

• Flat or exophytic papillary lesions

• Hyperkeratosis, parakeratosis,marked nuclear

• Mixed with basaloid type PeIN

Warty–basaloid penile intraepithelial neoplasia

In this variant, there is a variable mixture of warty and

basaloid cells. These mixed lesions tend to have a

spiking surface with koilocytic changes, whereas the

lower half of the epithelium is predominantly composed

of small basaloid cells.

Warty basaloid neoplasia

• Shares with warty SCC a higher association with

• Probable common pathogenesis:

• Warty – basaloid SCC is a recognized entity (>10%

Chaux et al Mod Pathol 23:896–904;2010

• Penile intraepithelial neoplasia (PeIN) is an

• HPV related and HPV unrelated lesions have

From the pathogenic point of view, penile cancers may be grouped in

Mean age 51 years

• 4%-10% of penile SCC

Chaux et al J.Urology 2010

• Shares with warty SCC a higher association with

• Probable common pathogenesis:

• Warty – basaloid SCC is a recognized entity (>10%

Chaux et al Mod Pathol 23:896–904;2010

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