Moderators: John R. Srigley and Rodolfo Montironi
Case 2 -
Carcinoma Cuniculatum of Penis
Antonio Cubilla MD
Institute de Patologia e Investigaticion
An 83-year-old patient presented with a foul smelling exophytic mass involving the distal portion of
the glans. The lesion was slowly-growing for the past 4 years. A biopsy revealed a well-differentiated
verrucous squamous cell carcinoma. A partial penectomy was performed.
Case 2 - Slide 1
Grossly there was a large white/gray granular exophytic mass involving the foreskin, coronal
sulcus and part of ventral and dorsal glans. The cut surface revealed irregular sinuses of tumor
invaginations from the surface to deep anatomical structures, corpora spongiosa and cavernosa with
fistula formation to the skin of the foreskin and shaft. The tumor grew along the tunica albuginea
forming a long tract.
Microscopically there was a labyrinthine burrowing pattern with surface fistulization. Individual
crypts had a jagged inner surface containing hyperkeratotic material and a sharply delineated external
border. The histological features resembled those of mixed verrucous- squamous cell carcinoma
(hyperkeratosis, papillomatosis, acanthosis, and squamous cell differentiation with lack of
koilocytosis). Deeply located keratin filled cyst-like spaces on serial gross sectioning were found to
be connected and continuous with either the crypts or the tumor surface. The interface between tumor and
stroma was sharply delineated or jagged with an invasive border.
Carcinoma cuniculatum of penis.
We recently found some penile tumors with a burrowing growth pattern similar to plantar
epithelioma cuniculatum described by Ayrd in 1954 .
Other sites affected are esophagus , jaw
oral cavity ,
nasal cavity and sinuses ,
abdominal wall ,
and intertriginous areas . They were also reported in
association with leprosy
pilonidal cysts, necrobiosis lipoidica  and chronic skin ulcers
Carcinoma cuniculatum of the penis is an unusual verruciform tumor characterized by a labyrinthine
exo- endophytic growth with irregular and deep sinusesand tracts simulating rabbits' burrows from
which this entity derives its name.
In our report of 7 cases 
affected patients were older males (rage of 73-83 years) in
comparison to the relatively younger age of patients with usual SCC (62 years), closer to the age of
patients with verrucous carcinoma (69 years)
 and similar to the age of
pseudohyperplastic SCC .
The duration of the disease prior to pathological diagnosis ranged from 12 to 60 months. At diagnosis
tumors were large (ave. 6.3 cm) , affecting multiple epithelial compartments (glans, coronal sulcus and
Grossly the outer surfaces of carcinoma cuniculata were indistinguishable from other verruciform
tumors but the cut surface was characteristic revealing deeply penetrating sinuses connecting the
surface with corpora spongiosa or cavernosa. Considering that superficial invaginations are not unusual
in low grade penile carcinomas we required for the diagnosis both a verruciform configuration and a deep
penetration beyond lamina propria. The deepest point of the tumor is a cul de sac equally broadly based
at the surface and in deeper areas. Microscopically the tumor showed some cytologic features of
verrucous carcinoma  but the overall growth pattern was different. There was an absence of
The differential diagnoses of carcinoma cuniculatum includes classical verrucous carcinoma, mixed
verrucous carcinoma and warty (condylomatous) carcinoma. We have recently reviewed a large number of
penile tumors originally classified as verrucous carcinoma and found the classical (pure) verrucous
carcinoma to be unusual. Most commonly we observed admixed with features of classical verrucous
carcinoma, a heterogeneous spectrum of morphological patterns: those of usual, papillary NOS, warty
(condylomatous) and sarcomatoid squamous cell carcinomas. The diagnosis of classical or "pure" verrucous
carcinoma should be restricted to neoplasms with extreme differentiation throughout, absence of
koilocytosis, and a broad base with sharply delineated base. Pure verrucous carcinomas in our experience
do not involve the corpus cavernosa. The deep penetration of carcinoma cuniculatum into corpora
cavernosa and the frequent presence of at least focally jagged invasive borders makes the distinction
possible. Carcinoma cuniculatum shares some features of mixed verrucous carcinoma but in addition shows
the characteristic sinuous burrowing pattern absent in mixed verrucous carcinomas. Another tumor with
a complex endophytic growth pattern which may be confused with carcinoma cuniculatum is the warty
carcinoma including the recently described endophytic "non invasive" variant . Warty
carcinoma is an uncommon HPV related tumor  that may be grossly indistinguishable from carcinoma
cuniculatum. Microscopically, especially in its endophytic variant, warty carcinoma may show an inverted
nodular growth of otherwise typical condylomatous papillae affecting lamina propria and corpus
spongiosum. Higher histologic grade and prominent koilocytotic atypia throughout the tumor aid to
differentiate warty carcinoma from carcinoma cuniculatum. Presence and absence of HPV has been reported
in carcinoma cuniculata
Rarely, metastases have been reported in carcinoma cuniculatum of the skin
but despite deep
invagination by tumors involving the tunica albuginea and corpora cavernosa in 6 cases, inguinal node
metastases were not present in our penile cases.
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