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Background
Penile carcinoma is a rare neoplasm, and the highest rates are found in developing countries. The relative frequencies of this tumor in Brazil and the United States is 2.1% and 0.5 respectively. By far, the most common histologic type is squamous cell carcinoma (SCC), which accounts for more than 95% of cases. There appears to be an association with Human Papilloma virus, similar to other genital tract cancers in women. These tumors are not usually painful but they form an large, usually fungating mass and may ulcerate.
OUTLINE
EPIDEMIOLOGY CHARACTERIZATION AGE RANGE-MEDIAN 6th decade
22% <40 yearsDeveloping countries especially Africa, Asia, and Latin America EPIDEMIOLOGIC ASSOCIATIONS CHARACTERIZATION Poor hygeine Lack of circumcision or late circumcision Venereal disease Present in about 7% of patients Cigarette smoking HPV Present in both neoplastic and pre-neoplastic lesions
Department of Pathology, Hospital General Universitario de Albacete and Universidad de Castilla la Mancha, Spain.
Sarcomatoid carcinomas are rare tumors predominantly composed of spindle cells. This report describes two cases of penile sarcomatoid carcinoma with similar clinicopathological findings. Distinctive features of these tumors were the focal immunostaining that showed the sarcoma-like cells with keratin, smooth muscle actin and p16, and the absence of immunostaining of these cells with p53, S100 protein and desmin. Polymerase chain reaction (PCR) using the GP5+/GP6+ set of primers was positive in both cases. The sequences of the amplified products showed that the implicated genotypes were Human papillomavirus (HPV) 16 and HPV18.
To the best of our knowledge, there has been no report in the English literature of HPV-associated penile sarcomatoid carcinoma.
These cases might represent an unusual presentation of dedifferentiated carcinoma in which HPV could be shown by a sensitive technique of PCR.Preferential association of human papillomavirus with high-grade histologic variants of penile-invasive squamous cell carcinoma.
Gregoire L, Cubilla AL, Reuter VE, Haas GP, Lancaster WD.
Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI 48201, USA.
J Natl Cancer Inst 1995 Nov 15;87(22):1705-9 Abstract quote
BACKGROUND: Human papillomavirus (HPV) is causally associated with cervical squamous cell carcinoma (SCC) and its precursor lesions. By analogy, HPV is believed to play a role in penile cancer through progression of HPV-associated penile squamous intraepithelial lesions (SIL). HPV DNA has been reported to be present in 100% of high-grade penile SIL, but the percentage of invasive or infiltrating penile SCC that was positive for HPV DNA has varied from study to study (positivity values ranging from 32% to 82%).
PURPOSE: To ascertain whether HPV is associated with penile cancer, we used a polymerase chain reaction (PCR)-based assay to test specimens of penile SCC for the presence of HPV DNA.
METHODS: A total of 117 formalin-fixed, paraffin-embedded specimens of penile cancer from an equal number of patients who had been diagnosed either at the Memorial Sloan-Kettering Cancer Research Center in New York City between 1964 and 1992 or the Universidad Nacional de Asuncion in Paraguay between 1980 and 1992 were analyzed. Specimens were examined without prior knowledge of the histology of the lesions. Methods were used that minimized sample contamination, thus avoiding false-positive results. PCR and Southern blot analyses were used to determine HPV type. The presence of HPV DNA was studied for association with the tumor properties histopathology, growth pattern, tumor grade, regional lymph node status, and anatomic location. Two-sided statistical tests were used to determine P values.
RESULTS: HPV DNA was detected in 26 (22.2%) of 117 specimens. In 23 (88.5%) of the 26 HPV-positive specimens, HPV type 16 (only) was identified. HPV DNA was frequently associated with SCC in areas showing basaloid and/or warty changes (nine [47.4%] of 19 specimens were HPV positive; P = .0125). More highly significant was the association of virus with basaloid SCC (nine [75%] of 12 specimens were HPV positive; P = .0005). However, HPV was not found to be associated with typical SCC of the penis (five [11.1%] of 45 specimens were HPV positive). Virus DNA was more often associated with high-grade tumors (P = .0278) exhibiting aggressive growth (P = .0382) localized to the glans penis (P = .0324). Stepwise logistic regression analysis revealed that only tumor histopathology was a significant predictor of an HPV association.
CONCLUSIONS: The presence of HPV DNA was found to be significantly associated only with those penile SCC exhibiting basaloid changes. Furthermore, HPV DNA sequences tended to be associated with higher grade and more aggressive tumor localized to the glans penis. The low frequency of HPV in penile SCC implies that only a small proportion of these cancers arise from HPV-associated penile SIL.
HIV Human papillomavirus-associated penile squamous cell carcinoma in HIV-positive patients.
Poblet E, Alfaro L, Fernander-Segoviano P, Jimenez-Reyes J, Salido EC.
Department of Pathology, Hospital S.V.S. Villajoyosa, Alicante, Spain.
Am J Surg Pathol 1999 Sep;23(9):1119-23 Abstract quote
Two cases of penile squamous cell carcinoma with distinctive clinicopathologic characteristics are presented. The tumors appeared in patients infected with HIV and were located in the glans of the penis. Histologically, the neoplasms were well-differentiated, infiltrating, squamous cell carcinomas. The entire spectrum from benign condyloma to infiltrative squamous cell carcinoma was present in the two patients. In both cases, human papillomavirus (HPV) could be demonstrated using polymerase chain reaction analysis.
The reported cases suggest a synergic interaction of HPV and HIV in the carcinogenic process of some penile carcinomas.
PATHOGENESIS CHARACTERIZATION FORESKIN TYPES
Preputial variability and preferential association of long phimotic foreskins with penile cancer: an anatomic comparative study of types of foreskin in a general population and cancer patients.Velazquez EF, Bock A, Soskin A, Codas R, Arbo M, Cubilla AL.
Am J Surg Pathol. 2003 Jul;27(7):994-8 Abstract quote Difficulty in foreskin retraction and phimosis are risk factors for penile carcinoma that may be related to the anatomically variable length of the foreskin. This observation has stimulated us to postulate the hypothesis that foreskin length is related to penile cancer. To compare the foreskin in the general population and patients with penile cancer, an anatomic classification of foreskin was designed.
We examined the foreskin of 215 uncircumcised males without cancer (age range 15-93 years) and the foreskin of 23 patients with cancer (age range 31-90 years). Foreskin types were classified as long (with the preputial orifice located beyond glans meatus and entirely covering the glans), medium (with the preputial orifice located between meatus and glans corona), and short (with the preputial orifice located between corona and coronal sulcus). Phimosis was defined as a nonretractable prepuce of the long type. We found that 77% of noncancer population cases had long foreskin and that only 7% of these cases were phimotic. Cancer patients showed long foreskin in 78% of the cases, and phimosis was significantly frequent in this group (52%) as compared with the other (p <0.001). Coexistence of a long foreskin and phimosis may explain the high incidence of penile cancer in some geographic regions.
To better document these findings, a comparison of foreskin types in countries with high and low incidence of penile cancer will be interesting. However, because phimosis appears to be a major factor, the presence of long foreskin may be a necessary but not a sufficient condition for cancer development.
For these reasons we support preventive circumcision in patients with long and phimotic foreskins living in high-risk areas. Cancers not related to long foreskins and phimosis may be causally different.HUMAN PAPILLOMA VIRUS Prevalence of human papillomavirus types 16 and 18 in squamous-cell carcinoma of the penis: a retrospective analysis of primary and metastatic lesions by differential polymerase chain reaction.
Wiener JS, Effert PJ, Humphrey PA, et al.
Int J Cancer 1992;50:694–701.
About 1/3 of all penile cancers harbor HPV-DNA to types 16 and 18
ONCOGENES Molecular pathology and clinicopathologic features of penile tumors: with special reference to analyses of p21 and p53 expression and unusual histologic features.
Lam KY, Chan KW.
Department of Pathology, The University of Hong Kong, Hong Kong.
Arch Pathol Lab Med 1999 Oct;123(10):895-904 Abstract quote
OBJECTIVES: To examine the histologic features of p21 in penile tumors and to determine the role of p21 and p53 in the pathogenesis of this group of tumors.
METHODS: The clinicopathologic features of 87 patients with penile tumors were studied. The expression of p53 and p21 proteins in 49 cases was investigated by immunohistochemistry.
RESULTS: Of the 87 tumors studied, 84 represented primary penile tumors (72 malignant and 12 benign) and 3 represented secondary tumors (2 from bladder, 1 from nasopharynx). The primary malignant penile tumors included 66 surface carcinomas with squamous differentiation (92%), 3 cases of Paget disease (4%), 1 case of Bowen disease (1%), and 2 penile urethral squamous cell carcinomas (3%). The former group was subdivided into squamous cell carcinoma (n = 50), verrucous carcinoma (n = 8), basaloid squamous cell carcinoma (n = 3), adenoid squamous cell carcinoma (n = 3), spindle cell carcinoma (n = 1), and adenosquamous carcinoma (n = 1). The benign tumors were squamous cell papillomas (n = 10) and fibromatoses (n = 2). Expression of p21 and p53 was noted in 40% and 89%, respectively, of the 47 patients with primary surface penile carcinoma with squamous differentiation. Positive p21 and p53 expression was also seen in 2 cases of Paget disease. Staining for p21 was often weak and was found in the suprabasal region of carcinomas with squamous differentiation, while p53 expression was seen in the basal region of squamous cell carcinomas. Preinvasive lesions also showed p21 and p53 expression. An inverse correlation between p53 and p21 expression (p53(+)/p21(-) or p53(-)/p21(+)) was noted in half of the squamous cell carcinomas, 4 of 5 verrucous carcinomas, 2 of 3 basaloid squamous cell carcinomas, and in 1 spindle cell carcinoma. The other cases did not show this correlation.
CONCLUSIONS: Penile tumors had different histologic variants and p21/p53 expression patterns. Expression of p21 did play a role in some tumors and could be dependent or independent of p53 expression.
GROSS APPEARANCE/
CLINICAL VARIANTSCHARACTERIZATION GENERAL Majority arise from the squamous epithelium covering the glans, foreskin, and coronal sulcus and may invade from one compartment to another
Glans is most common site
- Penile cancer.
Micali G, Nasca MR, Innocenzi D, Schwartz RA.
Department of Dermatology, University of Catania School of Medicine, Catania, Italy.
J Am Acad Dermatol. 2006 Mar;54(3):369-91; quiz 391-4. Abstract quote
Penile cancer, while relatively rare in the western world, remains a disease with severe morbidity and mortality, not to mention significant psychological ramifications. Furthermore, the disease is observed with dramatically increased incidence in other parts of the world.
A review of the literature has shown that the overwhelming majority of penile cancers are in situ or invasive squamous cell carcinomas, including a well-differentiated variant, verrucous carcinoma. Important predisposing factors are lack of circumcision, human papillomavirus infections, and penile lichen sclerosus, although other factors have occasionally been reported as well. Prevention, careful monitoring of patients at risk, and early diagnosis are essential to reduce the incidence of penile carcinoma and to provide a definitive cure. Public health measures, such as prophylactic use of circumcision, have proved successful but are controversial. Also, no standard therapeutic guidelines as to the best treatment strategy according to different stages, including efficacy of conservative nonsurgical modalities and indications for lymph nodal dissection, are available so far. It is common opinion that penile cancer is an emerging problem that deserves further investigations, and physicians, especially dermatologists, should be aware of this issue.
LEARNING OBJECTIVE: At the completion of this learning activity, participants should be familiar with penile carcinoma, its risk factors, its clinical and histologic presentation, and the treatments currently available for its management.Flat tumor
1/3 of all cancer of the glans and foreskin|
More than one epithelial compartment is involved in 60% of cases
Slightly elevated, white granular and firm tumor which may be ulcerated
Thickness varies from 1-10 mm and 2-3 cm in lateral extent
SCC in situ may be adjacent to invasive tumor20% are of this type
Large fungating and often ulcerated
Tumor extends into the corpora spongiosum or corpora cavernosa
Satellite nodules may be present
Direct extension to the preputial or shaft skin25% of cancers
Glans most common site
Large, granular white to gray tumors with a papillary configurationHistologically may have verrucous, warty, or papillary features
10-15% of cancers Two or more independent foci of cancers
Synchronous or metachronous
5% of cancers
Usually affect several epithelial compartmentsVARIANTS
HISTOLOGICAL TYPES CHARACTERIZATION GENERAL 70% are nonpapillary, nonkeratinizing squamous cell carcinomas
30% are additional histological subtypesAnatomic levels: important landmarks in penectomy specimens: a detailed anatomic and histologic study based on examination of 44 cases.
Cubilla AL, Piris A, Pfannl R, Rodriguez I, Aguero F, Young RH.
Instituto de Patologia e Investigacion, Asuncion, Paraguay.
Am J Surg Pathol 2001 Aug;25(8):1091-4 Abstract quote
The majority of squamous cell carcinomas of the penis arise from the glans, and the prognosis is related significantly to the depth of invasion of crucial anatomic landmarks. Accurate information related to this can only be obtained when specimens are carefully evaluated grossly. Most pathologists in developed countries encounter resected specimens of penile carcinoma infrequently, and gross evaluation is occasionally suboptimal, potentially preventing obtaining reliable prognostic information. The four distinct levels of the glans penis are the epithelium, lamina propria, corpus spongiosum, and corpus cavernosum.
A simple method for pathologic evaluation of the glans is presented.
Noteworthy findings in our study of a South American population were that the distance from the lamina propria to tunica albuginea ranged from 7 to 13 to 6 mm at the dorsal, central, and ventral areas of the corpus spongiosum, respectively. The most distal portion of the corpus cavernosum was located within the glans in 34 of 44 cases and in the body of the penis in only 10. The corpus spongiosum was thinner in the former cases.
These anatomic variations may bear on prognosis.
BOWENOID PAPULOSIS In the current WHO classification, this is not designated as a separate disease. Most investigators feel this is a variant of VIN
Clinically, these lesions are usually multiple and resmble seborrheic keratoses
Heterogeneity of human papillomavirus DNA in a patient with Bowenoid papulosis that progressed to squamous cell carcinoma.Park KC, Kim KH, Youn SW, Hwang JH, Park KH, Ahn JS, Kim YG, Kim SD, Lee DY, Choe JH, Chung JH, Cho KH.
Department of Dermatology, Seoul National University College of Medicine, Korea.
Br J Dermatol 1998 Dec;139(6):1087-91 Abstract quote Bowenoid papulosis (BP) of the genitalia, characterized by the histological findings of a squamous cell carcinoma, follows a largely benign clinical course. The detection of oncogenic human papilloma viruses (HPV) from BP points to an aetiological role of these viral infections.
A 47-year-old man with multiple genital skin lesions was seen over a 10-year period with the diagnosis of BP. Recently, he attended again with a recurrent genital tumour that was diagnosed as squamous cell carcinoma. His genital lesions progressed and became polymorphic in appearance, from a wart-like tumour to a reddish invasive plaque. To screen for the presence of different HPV sequences from different skin lesions and to correlate each HPV type with distinct clinical manifestations, polymerase chain reaction and single-strand conformational polymorphism (PCR-SSCP) were performed.
PCR-SSCP revealed the presence of several types of HPV from different genital lesions. Sequencing results disclosed that he had a mixed infection of HPV6b, HPV16, HPV18 and HPV33, respectively. Interestingly, the clinical findings were fairly well correlated with the oncogenic potential of HPV found from each lesion.
Development of squamous cell carcinoma by two high-risk human papillomaviruses (HPVs), a novel HPV-67 and HPV-31 from bowenoid papulosis.Yoneta A, Yamashita T, Jin HY, Iwasawa A, Kondo S, Jimbow K.
Departments of Dermatology and Urology, Sapporo Medical University School of Medicine, South 1 West 16, Chuo-ku, Sapporo 060-8543, Japan.
Br J Dermatol 2000 Sep;143(3):604-8 Abstract quote We report a patient with bowenoid papulosis (BP) involving two high-risk human papillomaviruses (HPVs) and the development of invasive squamous cell carcinoma (SCC).
Our patient showed verrucous lesions on the penis, perianal area and groin that had been noted over the previous 8 years and had recurred after all therapeutic approaches. The perianal and left inguinal lesions revealed invasive SCC on histology. HPV-31 and HPV-67 sequences were detected by polymerase chain reaction from BP lesions of the perianal area and the shaft of the penis. HPV-31 has already been reported in BP as a high-risk HPV for the development of SCC, but HPV-67 is a novel one that has never been reported in BP. As HPV-67 has sequence homology to HPV-52 and HPV-58, it belongs to the family of HPV-16, a high-risk HPV group.
Thus our patient showed two high-risk HPVs, i.e. HPV-31 and the novel HPV-67, which may be directly involved in the development of SCC.
Isolated human papillomavirus 18-positive extragenital bowenoid papulosis and idiopathic CD4+ lymphocytopenia.
Purnell D, Ilchyshyn A, Jenkins D, Salim A, Seth R, Snead D.
Department of Pathology, Walsgrave Hospitals NHS Trust, Coventry CV2 2DX, U.K.
Br J Dermatol 2001 Mar;144(3):619-21 Abstract quote We report a case of isolated extragenital bowenoid papulosis (BP) in a young man with an idiopathic low CD4 count. The lesions occurred on the dorsal aspect of his left middle finger and were not associated with genital involvement. Polymerase chain reaction studies of a biopsy demonstrated human papillomavirus 18.
As far as we are aware, this is the first documented case of BP (genital or extragenital) associated with idiopathic CD4 lymphocytopenia.
Extragenital bowenoid papulosis associated with atypical human papillomavirus genotypes.Papadopoulos AJ, Schwartz RA, Lefkowitz A, Tinkle LL, Janniger C, Lambert WC.
Dermatology, Pediatrics and Pathology, New Jersey Medical School, Newark, New Jersey, USA.
J Cutan Med Surg 2002 Mar-Apr;6(2):117-21 Abstract quote BACKGROUND: Bowenoid papulosis typically appears as grouped violaceous or red-brown papules in the genital or perianal regions and clinically resembles condylomata acuminata. Isolated extragenital bowenoid papulosis is rare and has been reported in only a few case reports.
OBJECTIVES: A 51-year-old immunocompetent, healthy woman had two solitary papules on the elbow; a 41-year-old HIV-positive man had a solitary cutaneous plaque on the abdomen. No genital, periungual, or other extragenital sites of involvement were noted in either patient. The diagnosis was confirmed histologically in both cases. Lesional skin from the female patient was tested with the Digenehybrid HPV DNA assay and was positive for a mixture of low-risk HPV subtypes (6, 11, 42, 43, 44). Lesional skin from the male patient was tested with polymerase chain reaction (PCR). Consensus primers targeted for the HPV L1 region, which is a highly conserved sequence common to more than 20 HPV subtypes encoding a viral capsid protein, were used. PCR using the consensus primers was positive, but type-specific probes for HPV types 6, 11, 16, 18, 45, 31, 33, 35, and 39 were negative.
CONCLUSIONS: To our knowledge, our male patient represents the first case of isolated bowenoid papulosis of the abdominal skin. Isolated upper-extremity bowenoid papulosis in our female patient is also a unique case in both location and involvement of low-risk HPV types (6, 11, 42, 43, 44), which have not been previously associated with extragenital bowenoid papulosis.
PRECURSOR LESIONS
- Epithelial abnormalities and precancerous lesions of anterior urethra in patients with penile carcinoma: a report of 89 cases.
Velazquez EF, Soskin A, Bock A, Codas R, Cai G, Barreto JE, Cubilla AL.
1Department of Pathology, New York University Medical Center, New York, NY, USA.
Mod Pathol. 2005 Jul;18(7):917-23. Abstract quote
Urethral and penile tissues and their neoplasms are considered anatomically and pathogenetically different. Since we observed urethral dysplastic lesions and some similarities between noninvasive and invasive lesions of the anterior urethra and glans, we designed this study to document epithelial urethral abnormalities in patients with penile squamous cell carcinoma.
We examined urethral epithelia from 170 penectomies with invasive squamous cell carcinoma finding a variety of primary epithelial abnormalities in 89 cases (52%) and secondary invasion of penile carcinoma to urethra in 42 cases (25%). Patients' average age was 68 years. Primary tumors measured 4 cm in average diameter and the majority were squamous cell carcinoma of the usual (67%) or verrucous type (15%). Primary epithelial abnormalities found were squamous intraepithelial lesions, metaplasias and microglandular hyperplasias. Urethral squamous intraepithelial lesions of high grade was found in six patients and of low grade in eight cases. Squamous metaplasia, seen in 69 cases, was the most frequent finding. Metaplasias were classified as nonkeratinizing and keratinizing. Nonkeratinizing metaplasias (57 cases) were variegated in morphology: simplex (26 cases), hyperplastic (12 cases), clear cell (11 cases) and spindle (8 cases). Keratinizing metaplasias (12 cases) showed hyperkeratosis and were more frequently associated with verrucous than nonverrucous penile squamous cell carcinoma. Microglandular hyperplasia was present in eight cases. Lichen sclerosus was associated with simplex squamous metaplasia in four cases. Despite the large size of the primary tumors, direct urethral invasion by penile carcinoma was present in only 25% of the cases.
The presence of precancerous lesions in urethra of patients with penile carcinoma indicates urethral participation in the pathogenesis of penile cancer. Simplex squamous metaplasia is a common finding probably related to chronic inflammation. Keratinizing and hyperplastic squamous metaplasias may be important in the pathogenesis of special types of penile carcinomas such as verrucous carcinoma.VARIANTS OF CARCINOMA SQUAMOUS CELL CARCINOMA, USUAL TYPE Majority are well to moderately differentiated
73% well
27% moderate
May have adjacent squamous cell carcinoma in situ
May have clear cell changes or acantholysis, the latter usually with higher grade tumorsADENOSQUAMOUS CARCINOMA BASALOID CARCINOMA 10% of cancers
33-84 years (Average 55 years)
Usually presents with a large mass in glans with secondary involvement of the coronal sulcus and foreskin
Often 4 cm or more with ulceration
2/3 have enlarged positive inguinal nodes
9/16 dead of disease <3 years
3/16 Alive with disease up to 38 months after diagnosis
3/16 free of disease
1/16 died of other causesFrequently vertical growth with closely packed nests and comedonecrosis
Numerous mitoses
Small poorly differentiated cells with rare peripheral palisading and focal keratinization
Perineural and vascular invasion frequentBasaloid squamous cell carcinoma: a distinctive human papilloma virus-related penile neoplasm: a report of 20 cases.
Cubilla AL, Reuter VE, Gregoire L, Ayala G, Ocampos S, Lancaster WD, Fair W.
Instituto de Anatomia Patologica, Facultad de Ciencias Medicas, Universidad Nacional de Asuncion, Paraguay.
Am J Surg Pathol 1998 Jun;22(6):755-61 Abstract quote
Most penile neoplasms are squamous cell carcinomas (SCC), but there are subtypes that show morphologic and possibly etiologic differences. Clinicopathologic features of 20 patients with basaloid carcinoma (BC), an unusual variant of squamous cell carcinoma, are presented.
Median age was 52 years, and all tumors were located in the glans, three confined to the perimeatal region. Average tumor size was 3.8 cm. Microscopically, nests of small, basophilic cells with numerous mitosis were present. Human papillomavirus DNA sequences (type 16), using the polymerase chain reaction (PCR), were found in 9 of 11 cases. Differential diagnosis included urethral transitional cell, basal cell, small cell neuroendocrine, and metastatic carcinoma. Factors more significantly associated with regional metastasis and mortality were tumor thickness greater than 10 mm and infiltration of the corpus cavernosum.
A comparison with typical squamous cell carcinoma showed basaloid carcinoma to have a higher histologic grade, a deeper invasion of penile anatomic levels, and a higher mortality rate. Of 17 patients observed, 10 were dead of disease (average time, 34 months), one was alive with disease 6 months after diagnosis, and 5 were alive and free of disease (average time, 71 months); the remaining patient died of other causes. Basaloid carcinoma is a distinctive morphologic subtype of squamous cell carcinoma frequently associated with the human papilloma virus.
CARCINOMA CUNICULATUM
*Instituto de Patologia e Investigacion and Facultad de Ciencias Medicas, Universidad Nacional de Asuncion, Asuncion, Paraguay daggerDepartment of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
We are reporting a peculiar variant of penile squamous cell carcinoma (SCC) characterized by its peculiar deeply penetrating and burrowing pattern of growth. This low grade, verruciform penile neoplasm is similar to the plantar epithelioma cuniculatum originally described by Ayrd in 1954.
Clinical and pathologic features of 7 patients are presented. There were 7 partial penectomies and 4 bilateral inguinal node dissections. The mean patient's age was 77 years. Grossly, the tumors were white to gray, exo-endophytic, and papillomatous with a cobblestone or spiky appearance. All cases affected the glans and extended to coronal sulcus and foreskin (average size was 6.3 cm).
The hallmark of the lesion was noted on cut surface where there were deep tumoral invaginations forming irregular, narrow, and elongated neoplastic sinus tracts connecting the surface of the neoplasm to deep anatomic structures. The neoplasm invaded through lamina propria and corpus spongiosum and grew along the loose connective tissue of Buck fascia to involve the tunica albuginea and corpora cavernosa (average depth was 32 mm). Deeply invasive keratin filled cysts or crypts, on serial sections, showed to be connected to the surface tumor. Fistulization to the skin was also noted. Microscopically, the lesions corresponded to well-differentiated carcinomas with bulbous front of invasion. There were focal areas of higher histologic grade and more infiltrative and jagged borders in 4 cases. Inguinal nodes were negative in 4 patients in which groin dissection was performed.
Carcinoma cuniculatum is a variant of penile SCC with distinctive growth pattern and should be distinguished from other verruciform tumors such as the verrucous, papillary, and warty carcinomas. Unlike most subtypes of penile SCCs and despite the deep invasion, none of the tumors showed groin or systemic dissemination at time of diagnosis.CLEAR CELL
- Penile clear cell carcinoma: a report of 5 cases of a distinct entity.
Liegl B, Regauer S.
From the Institute of Pathology, Medical University of Graz, Graz, Austria.
Am J Surg Pathol. 2004 Nov;28(11):1513-7. Abstract quote
We present a series of 5 penile clear cell carcinomas, which arose in middle-aged men at the inner side of the foreskin. They were large, exophytic, partly ulcerated, and widely invasive tumors with sharp demarcation to the surrounding normal skin/mucosa.
Histologically, they were composed of large clear cells with intracytoplasmic PAS/d-PAS-positive material and showed extensive lymphatic and blood vessel invasion. Strong staining with antibodies to Muc-1, EMA, and CEA was typical. All carcinomas harbored HPV16 DNA, although only one carcinoma revealed HPV-related cytologic cell changes. All 5 patients had extensive, partly cystic inguinal lymph node metastases with a striking clear cell differentiation and focal dense sclerotic basement membrane material, either at or within several months after initial diagnosis. Two patients are alive without disease after 7 and 10 years. One patient died after 9 months of widespread disease and 2 patients are presently alive at 7 and 17 months follow-up with widespread lymphatic and hematogenous metastases despite adjuvant chemo- and radiation therapy. In contrast to squamous cell carcinoma, penile clear cell carcinomas show extensive blood and lymph vessel invasion and early metastases to regional lymph nodes.
Clear cell carcinomas represent a distinct group of penile cancers that may have a different clinical behavior than usual penile squamous cell carcinomas.PAPILLARY Most common verruciform cancers
Average age 60 years
Most common on glans and foreskin
Large cauliflower gray-white granular tumors
Papillary with acanthosis and hyperkeratosisPSEUDO-HYPERPLASTIC Pseudohyperplastic Squamous Cell Carcinoma of the Penis Associated With Lichen Sclerosus. An Extremely Well-differentiated, Nonverruciform Neoplasm That Preferentially Affects the Foreskin and Is Frequently Misdiagnosed: A Report of 10 Cases of a Distinctive Clinicopathologic Entity.
Cubilla AL, Velazquez EF, Young RH.
*Instituto de Patologia e Investigacion and Facultad de Ciencias Medicas, Asuncion, Paraguay; the daggerNew York University Medical Center, New York, NY; and double daggerThe James Homer Wright Pathology Laboratories of Massachusetts General Hospital, Harvard Medical School, Boston, MA.
Am J Surg Pathol. 2004 Jul;28(7):895-900. Abstract quote
We present 10 cases of well-differentiated, squamous cell carcinoma of the penis with pseudohyperplastic features. At presentation, the median age was 69 years. Seven of the tumors were multicentric, and the majority preferentially involved the foreskin inner mucosal surface. Grossly the tumors were typically flat or slightly elevated, white and granular, and measured approximately 2 cm. Characteristic histologic features included keratinizing nests of squamous cells with minimal atypia surrounded by a reactive fibrous stroma. In biopsies or individual areas of resected specimens, the differential diagnosis with pseudoepitheliomatous hyperplasia was difficult but when samples of adequate size were available, obvious evidence of infiltration was present. The adjacent squamous epithelium typically showed changes that are known to be associated with squamous cell carcinoma ranging from squamous hyperplasia to low-grade, and in a few cases high-grade, squamous intraepithelial lesions. Well-developed lichen sclerosus was seen in all cases. Patients were treated by circumcision or partial penectomy.
With the exception of 1 patient who developed a glans recurrence 2 years after initial circumcision, follow-up after the initial surgical procedure has been uneventful. The majority of penile carcinomas with the high degree of differentiation seen in these cases are in the category of the verruciform tumors, either the verrucous or papillary carcinoma, not otherwise-specified subtypes.
Experience with the cases reported in this series indicates that a subset of nonverruciform, often multicentric, tumors with a high degree of differentiation and pseudohyperplastic features occur and preferentially involve the foreskin. Because it was present in all cases, lichen sclerosus may play a precancerous role.RHABDOID
Squamous cell carcinoma of the penis with rhabdoid features.Urdiales-Viedma M, Fernandez-Rodriguez A, De Haro-Munoz T, Pichardo-Pichardo S.
Departments of Pathology and Urology, Unidad de Anatomia Patologica, Hospital San Juan de la Cruz, Ubeda, Jaen, Spain.
Ann Diagn Pathol 2002 Dec;6(6):381-4 Abstract quote A 76-year-old man presented with a tumoral lesion in his penis that had all the light microscopic and immunohistochemical features of a squamous cell carcinoma with rhabdoid phenotype. We believe that this is the fourth reported case of squamous cell carcinoma with rhabdoid features and the first one located in the penis. Rhabdoid cells were primarily located in areas with an alveolar pattern, most of them being isolated and intermixed with necrotic cells and necrotic debris.
We suggest that the rhabdoid phenotype could represent a type of degeneration, or a preliminary stage before apoptosis or cell necrosis, instead of a specific differentiation. In extrarenal tumors with rhabdoid features, stage and histologic types of tumors where rhabdoid changes occur are the most important prognostic factors.
SARCOMATOID 1% of penile cancers
Malignant spindle cells arranged in fascicles and bundles
- Sarcomatoid Carcinoma of the Penis: A Clinicopathologic Study of 15 Cases.
Velazquez EF, Melamed J, Barreto JE, Aguero F, Cubilla AL.
From the Departments of *Dermatology and daggerPathology, New York University Medical Center, New York, NY; and double daggerInstituto de Patologia e Investigacion, Asuncion, Paraguay.
Am J Surg Pathol. 2005 Sep;29(9):1152-1158. Abstract quote
Sarcomatoid carcinomas are uncommon, high-grade tumors, predominantly composed of spindle cells. Only a few cases arising in the penis have been reported.
The aim of this study is to better define the clinicopathologic features of this neoplasm. A total of 400 cases of squamous cell carcinoma of the penis were reviewed from which 15 sarcomatoid carcinomas (4%) were identified. Clinical and pathologic features were evaluated in all cases. Immunohistochemical studies for expression of AE1/AE3, Cam 5.2, 34betaE12, EMA, vimentin, muscle specific actin, smooth muscle actin, desmin, S-100, p63, and p53 and in situ hybridization studies for HPV were performed in 5 cases. Information about lymph node status was available in 9 cases, and follow-up in 5 cases. The mean age was 59 years, and mean tumor size was 5 cm.
Grossly, most tumors were large, polypoid, and ulcerated masses frequently affecting the glans (93%) and deeply invading corpora cavernosa (80%) and skin. Microscopically, the lesions were predominantly composed of atypical spindle cells disposed in interlacing fascicles, resembling fibrosarcoma or leiomyosarcoma, sometimes admixed with pleomorphic giant cells mimicking malignant fibrous histiocytoma. One case was predominantly composed of myxoid areas. Less frequent and focal patterns were pseudoangiomatous and epithelioid. Mitotic figures were numerous, and necrosis was prominent. Foci of heterologous differentiation toward bone (osteosarcomatous component) were present in 1 case. Four cases showed a minor mixed component of usual, papillary, verrucous, and basaloid carcinoma. Intrapenile metastasis ("satellitosis") was present in 4 tumors. One of the cases was multicentric with a separate independent focus of well-differentiated carcinoma with pseudohyperplastic features. Associated low- and high-grade squamous intraepithelial lesions were noted in 73% of the cases.
Immunohistochemical studies and HPV in situ hybridization were done in 5 cases. The spindle cells were diffusely positive for vimentin and p53 and showed at least intermediate expression of 34betaE12 and p63 in all cases. EMA and AE1/AE3 were focally positive in 60% of the cases, and Cam 5.2 was focally positive in 1 case. Tumor cells failed to express muscle specific actin, smooth muscle actin, desmin, and S-100. HPV in situ hybridization was negative in all cases. Inguinal metastases were present in 89% of the cases. Two of five patients with adequate follow-up died of disease within 8 months of the diagnoses.
In conclusion, penile sarcomatoid carcinomas are unusual, large, and aggressive tumors usually associated with lymph node metastasis and poor outcome. Differential diagnoses include sarcoma and melanoma. Cytokeratin 34betaE12 and p63 appear to be the more specific and sensitive markers to categorize these tumors as epithelial. Diffuse immunoreactivity for p53, compared with a more basal and focal reactivity in differentiated squamous cell carcinoma, may be indicative of a late mutation in the natural progression of the disease.VERRUCOUS 3% of all penile cancers
20% or verruciform cancers
Exophytic white gray tumor usually about 3 cm in diameter
Glans most common siteProminent papillomatosis and hyperkeratosis
Well differentiated
Base of tumor is broad with pushing regular borders
1/3 recur due to insufficient surgeryWARTY (Condylomatous) carcinoma Low grade tumor, slow growing with cauliflower-like appearance averaging 4 cm
Median age 61 years
6% of tumors and 35% of verruciform tumors
Glans most common site
Inguinal lymph node mets infrequentLong papillae with fibrovascular core with undulating appearance
Prominent hyper and parakeratosis
Koilocytes numerous
Grade 1 or 2 histologyWarty (Condylomatous) Squamous Cell Carcinoma of the Penis A Report of 11 Cases and Proposed Classification of `Verruciform' Penile Tumors
Antonio L. Cubilla, M.D.; Elsa F. Velazques, M.D.; Victor E. Reuter, M.D.; Esther Oliva, M.D.; Martin C. Mihm Jr., M.D.; Robert H. Young, M.D.
From Instituto de Patologia e Investigacion and Facultad de Ciencias Medicas, Asuncion, Paraguay (A.L.C.); Department of Pathology, New York University, New York, New York, U.S.A. (E.F.V); Department of Pathology, Memorial Sloan-Kettering Cancer Center, Cornell University Medical College, New York, New York, U.S.A. (V.E.R); James Homer Wright Pathology Laboratories, Massachusetts General Hospital and Department of Pathology, Harvard Medical School, Boston, Massachusetts, U.S.A. (E.O., M.C.M., R.H.Y.).
Am J Surg Pathol 2000;24:505-512 Abstract quote
Within the spectrum of penile squamous cell carcinomas, those that we descriptively refer to collectively as the ``verruciform'' lesions are particularly difficult to subclassify.
In a review of 50 such tumors, we found 11 distinctive neoplasms with condylomatous features conforming to the appearance of so-called ``warty (condylomatous) carcinoma.''
The average patient age was 55 years and the average duration of disease was 19 months. The primary tumor involved multiple anatomic sites (glans, coronal sulcus, and foreskin) in seven cases and a single site (glans or foreskin) in four cases. Grossly, white to gray cauliflower-like tumors typically measuring approximately 5 cm were noted.
Histologically the tumors were mainly papillomatous with acanthosis and hyperkeratosis. The papillae had prominent fibrovascular cores. The most conspicuous microscopic findings were striking nuclear atypia of koilocytotic type and clear cytoplasm. The interface between tumor and stroma was irregular in the majority of cases; deep invasion of corpus cavernosum was noted in five cases.
The differential diagnosis included verrucous carcinoma, low-grade papillary squamous cell carcinoma, not otherwise specified, and giant condyloma acuminatum. Among other differences, the first two lesions show no koilocytotic changes and the last lacks malignant features and irregular stromal invasion.
Metastatic spread occurred in two patients; both are alive with evidence of recurrent disease 12 and 72 months after initial diagnosis. A third patient was alive with recurrent disease 12 months after diagnosis. Five patients were free of disease 8, 12, 24, 52, and 108 months after diagnosis. Three patients were lost to follow up.
Warty (condylomatous) carcinomas of the penis are morphologically distinctive verruciform neoplasms with features of human papillomavirus-related lesions and should be distinguished from other verruciform tumors so that differences in behavior, if any, between these tumors will become established.
Clinicopathologic Features and Human Papillomavirus DNA Prevalence of Warty and Squamous Cell Carcinoma of the Penis
Artur L. R. Bezerra, etal.
Am J Surg Pathol 2001;25:673-678 Abstract quote
Squamous cell carcinoma (SCC) accounts for 95% of penile malignant neoplasms. A subtype of SCC, named warty carcinoma (WC), is a morphologically distinct verruciform tumor with features of human papillomavirus (HPV)-related lesions. Descriptions of the behavior and histologic features of this tumor are scarce in the literature.
The aim of this report is to analyze the clinicopathologic features and HPV deoxyribonucleic acid status in 60 SCCs and 11 WCs. The mean patient age was 46.5 ± 15.9 years for WC and 52.6 ± 12.4 years for SCC. No significant differences in age (p = 0.154) and clinical staging (T, p = 0.649; N, p = 0.497) between the two groups of tumors were found. When compared with SCCs, WCs exhibited less lymphatic embolization (p = 0.001), nodal metastasis (p = 0.019), and corpora cavernosa and corpus spongiosum infiltration (p = 0.040). Lymph node metastases were found in 34 of 60 SCC patients (56.7%) and in two of 11 WC patients (18.2%). No patients with WC tumors died of the disease compared with 19 of 60 (5-year specific survival, 66.0%) in the SCC group (p = 0.032). HPV deoxyribonucleic acid was more likely to be associated with WC (five of 11, 45.5%) than SCC (16 of 60, 26.7%), although significance was not reached (p = 0.209).
The results suggest that WC is less aggressive and confers a better prognosis than typical SCC of the penis.
DIFFERENTIAL DIAGNOSIS KEY DIFFERENTIATING FEATURES* Metastatic epidermotropic squamous carcinoma histologically simulating primary carcinoma.
Youngberg GA, Berro J, Young M, Leicht SS.
Department of Pathology, East Tennessee State University College of Medicine, Johnson City.
Am J Dermatopathol 1989 Oct;11(5):457-65 Abstract quote
We present a case of a patient with penile squamous carcinoma and unilateral inguinal nodal involvement.
Histological sections of the inguinal tumor demonstrated a basaloid (small-cell) squamous carcinoma of the type that arises from modified skin or mucosa. Multiple cutaneous lesions subsequently developed in the ipsilateral lower extremity. Biopsies revealed tumor that had the same histologic appearance as the nodal metastasis but that also showed a smooth and continuous connection with the overlying epidermis. We discuss the significance of this finding and review the pertinent literature.
GIANT CONDYLOMA WARTY CARCINOMA VERRUCOUS CARCINOMA PAPILLARY CARCINOMA, NOS Papillae Arborizing, non undulating, rounded Long and undulating, condylomatous complex Straight Variably complex Fibrovascular cores Prominent Prominent Rare Present Base Regular, broad, and pushing Rounded or irregular and jagged Regular, broad, and pushing Irregular and jagged Grade I I/II I I//II Koilocytotic atypia Present at surface Prominent and diffuse Absent Absent Metastasis No Yes No Yes
PROGNOSIS AND TREATMENT CHARACTERIZATION Prognostic Factors Involvement of the skin of the shaft usually correlates with infiltration of the corpora cavernosa
Verruciform growth
Foreskin tumorsVertical growth
Tumors of glans or coronal sulcus
Poorly differentiated tumors
Invasive tumorsPositive Resection Margins in Partial Penectomies: Sites of Involvement and Proposal of Local Routes of Spread of Penile Squamous Cell Carcinoma
Velazquez, Elsa F MD*; Soskin, Ana MD†; Bock, Adelaida MD†; Codas, Ricardo MD†; Barreto, Jose E MD‡; Cubilla, Antonio L MD†‡
From the *New York University Medical Center, New York, NY; †Facultad de Ciencias Medicas, Universidad Nacional de Asuncion; and ‡Instituto de Patologia e Investigacion, Asuncion, Paraguay.
American Journal of Surgical Pathology : Volume 28(3) March 2004 pp 384-389 Abstract quote Recurrence in patients with penile carcinoma occurs in about one third of cases, usually due to insufficient surgery or positive resection margins. An evaluation of surgical resection margins in penectomy specimens was performed to determine precise anatomic sites of tumor involvement, hoping to advance knowledge concerning the local routes of spread of penile carcinomas.
A pathologic study of 80 partial penectomies revealed 14 positive margins. Margins were examined after their separation from the main specimen as follows: 1) proximal urethra and surrounding tissues consisting of urethral epithelium with Litree glands, lamina propria, corpus spongiosum, and penile fascia (periurethral cylinder); 2) proximal shaft with corresponding corpora cavernosa separated and surrounded by the tunica albuginea and penile fascia; and 3) skin of shaft with underlying corporal dartos. In 9 patients, only one site was involved by carcinoma, and in 5 there were multiple contiguous sites (for a total of 20 anatomic sites).
The distribution of the various sites involved by carcinoma was as follows: urethral epithelium, 4 cases (2 in situ and 2 invasive carcinomas including intraluminal spread); lamina propria, 5 cases; corpus spongiosum, 3 cases; penile fascia, 6 cases; and corpora cavernosa and skin, 1 case each. One of the in situ lesions was discontinuous with the main glans tumor, and the other one was continuous with it. The penile fascia was the most commonly involved site followed by the urethral lamina propria and epithelium. Dissemination to outer skin, corpora cavernosa, and corpus spongiosum was less frequent. The highly vascularized and innervated loose connective tissue of the penile fascia appears to facilitate tumor spread. The urethra is either a pathway for in situ tumor progression from glans to urethra or part of a field prone to malignant transformation. The infrequent involvement of corpora cavernosa is probably due to the tunica albuginea acting as a barrier preventing tumor spread.
Based on these observations and the examination of hundreds of penectomy specimens, we are proposing five probable routes of local spread for penile cancer: 1) horizontal and superficially spreading from one epithelial mucosal compartment (glans, coronal sulcus, and foreskin) to the other; 2) following the penile fascia; 3) through spaces created by feeding vessels in the tunica albuginea; 4) vertical spreading involving step-by-step different penile anatomic compartments; and 5) along the urethral epithelium.Predicting Cancer Progression in Patients with Penile Squamous Cell Carcinoma: The Importance of Depth of Invasion and Vascular Invasion
Robert E. Emerson, M.D., Thomas M. Ulbright, M.D., John N. Eble, M.D., William A. Geary, M.D., Ph.D., George J. Eckert, M.S. and Liang Cheng, M.D.
Departments of Pathology (REETMU, JNE, WAG, LC) and Biostatistics (GJE), Indiana University School of Medicine, Indianapolis, Indiana
Mod Pathol 2001;14:963-968 Abstract quote
The ability to predict cancer progression may help the clinical management of patients with penile squamous cell carcinoma.
We studied 22 cases of squamous cell carcinoma of the penis diagnosed between 1989 and 1998.
The depth of invasion was measured from the basement membrane of the squamous epithelium to the deepest invasive cancer cells. Cancer progression was defined as the development of lymph node metastasis or distant metastasis. The mean patient age was 63 years and the mean follow-up was 28 months. Ten patients developed cancer progression. The mean depth of invasion among patients with cancer progression was 9.8 mM, as compared to the mean depth of invasion of 4.0 mM among those patients without cancer progression (P = .02). Vascular invasion was also predictive of cancer progression (P = .02). Metastases developed in the majority (6 out of 7) of cases invading more than 6 mM, but developed only in a minority (4 out of 15) of cases invading 6 mM or less.
We conclude that depth of invasion and vascular invasion are significant predictors of cancer progression for penile squamous cell carcinoma.
Metastasis Inguinal lymph nodes Dependent upon site and growth pattern:
Circumcision for cancer of the foreskin
Partial penectomy vs. total penectomyPenile cancer: a case for guidelines.
Munro NP, Thomas PJ, Deutsch GP, Hodson NJ.
Department of Urology, Royal Sussex County Hospital, Brighton, UK.
Ann R Coll Surg Engl 2001 May;83(3):180-5 Abstract quote
INTRODUCTION: Aspects of the management of penile cancer remain controversial. In the management of early T1 N0 disease, treatments are divided between amputation and a variety of penis conserving techniques (PCT); local excision, laser techniques, chemotherapy and radiotherapy. We report on a retrospective series of patients with penile cancer.
PATIENTS AND METHODS: Thirty-seven patients were diagnosed between 1987-1996. All patients records were retrieved. Data recorded included TNM stage, histological grade and treatment. The end-points were death, nodal progression and local recurrence.
RESULTS: Median survivor follow-up of 42 months was obtained. Twenty-six patients (70%) presented with T1 disease, 7 (19%) T2 and 4 (11%) T3 or T4. Inguinal nodal disease was seen in 11 (30%). The mean age was 63 years. Overall, 13 penile amputations were performed, 13 underwent radiotherapy, 6 were locally excised in combination with radiotherapy and 3 underwent local excision alone. Two patients were unsuitable for treatment. Of the total (37 patients) 15 have died; 12 from penile cancer. Ten have suffered disease progression and 12 remain alive with no evidence of disease. Twenty-three patients presented with early T1 NO disease. They were treated with radiotherapy (12), local excision (2), combined radiotherapy and excision (2) and partial amputation (4). Outcome was not significantly related to treatment modality. Spread to the inguinal nodes or local recurrence has occurred in 10, of whom 2 have died. Only 13 (57%) appear disease-free.
CONCLUSIONS: The characteristics of the patients and the disease in this series are similar to published series in Europe and North America. There is significant variability in the modalities of treatment used within this series. Local recurrence and disease progression occurs in 43% of T1 N0 lesions. There would seem to be some room for improvement. International data are retrospective and inconclusive with regard to best practice. There is an urgent requirement for randomised controlled trials to improve the outcome of these patients.
The treatment of penile carcinoma: experience in 64 cases.
Demkow T.
Department of Urology, Maria Sklodowska-Curie Cancer Centre, Warsaw, Poland.
Int Urol Nephrol 1999;31(4):525-31 Abstract quote
INTRODUCTION: Carcinoma of the penis is an uncommon entity in Poland (160 new cases per year).
PURPOSE: To review our results in treatment of penile cancer in 64 patients.
MATERIAL AND METHODS: From 1989 to 1998, 64 patients were treated for carcinoma of the penis. The age of the patients varied from 21 to 86. Clinical and pathological categories were assessed according to TNM classification. Inguinal lymphadenectomy was performed in 35 patients. Following surgery 12 patients underwent radiotherapy, 3 chemotherapy, 3 radiotherapy and chemotherapy.
RESULTS: Twenty-two percent of patients died of cancer with median survival of 49 weeks. Bilateral inguinal involvement after node dissection was found in 17 patients. Unilateral inguinal involvement was found in 7 patients. Six patients had positive pelvic nodes. Of patients with initially non metastatic disease (N0) 8.3% showed progression to death, of patients with initially lymph node metastases (N+) 46% showed progression to death. The 5-year disease-free survival rates of patients with N+ and N0 were 40% and 82%, respectively. Of the patients 11% had local recurrence. Postoperative complications developed in 30 cases.
CONCLUSIONS: The likelihood of lymph node invasion at presentation was related to T category and grade of primary tumour. The most important prognostic factor for patients with carcinoma of the penis was lymph node involvement
Surgical treatment of penile carcinoma: our experience from 1976 to 1997.
Ficarra V, D'Amico A, Cavalleri S, Zanon G, Mofferdin A, Schiavone D, Malossini G, Mobilio G.
Department of Urology, University of Verona, Italy.
Urol Int 1999;62(4):234-7 Abstract quote
OBJECTIVE: The purpose of this work is to evaluate our experience with the surgical treatment of penile squamous carcinoma, analyzing the therapeutic results in terms of local recurrence rates, survival and mortality rates.
MATERIAL AND METHODS: From 1976 to 1997, 47 patients were treated at our institution for carcinoma of penis. Treatment of primary tumor was conservative in 8 patients (17%). Partial penectomy was performed in 30 patients (63.8%); total penectomy in 5 (10.7%) and emasculation in 4 (8.5%). Pathological stage was pTis in 2 cases (4.2%), pT1 in 20 (42.6%), pT2 in 21 (44. 7%) and pT3 in 4 (8.5%). The tumor was clinically overstaged in 13 patients (27.7%) and understaged in 4 (8.5%). Bilateral inguinal lymphadenectomy was performed only in 4 patients clinically N+ (pN2) and in 3 clinically N0 (pN0).
RESULTS: Local recurrence rate was 43% in the patients with pT1 stage tumor treated conservatively. No local recurrence was observed after penectomy. 19 patients (40.4%) are alive and disease-free; 17 patients (36.2%) died of the tumor and 11 patients (23.4%) died of other causes but disease-free. Mean follow-up is 69.43 months. The overall 5-year survival rate was 34%.
CONCLUSION: Partial penectomy gives better results than conservative treatment in the local management of the T1 stage tumor. Survival and mortality rates are related to both pathological and histological stages. The high mortality rate observed in the pT2 stage tumors in our experience might be related to the fact that in this stage an inguinal lymphadenectomy was not performed as a rule.
Iridium-192 interstitial therapy for squamous cell carcinoma of the penis.
Delannes M, Malavaud B, Douchez J, Bonnet J, Daly NJ.
Department of Radiation Oncology, Centre Claudius Regaud, Toulouse, France.
Int J Radiat Oncol Biol Phys 1992;24(3):479-83 Abstract quote
From February 1971 through February 1989, 51 patients with biopsy proven epidermoid carcinoma of the penis were treated with interstitial therapy (Iridium 192).
The breakdown according to the stage was T1s = 3, T1 = 14, T2 = 28, T3 = 6, N0 = 43, N1 = 7, N2 = 1. The dose ranged from 50 to 65 Gy (mean: 60 Gy). Patients without clinical nodal involvement received no treatment to the nodes. Stage N1 and N2 patients had surgery and external irradiation to the inguinal and iliac nodes. Six of fifty-one (12%) patients developed nodal and/or metastatic disease following therapy. Five of six presented initially with clinical nodal involvement. Seven of fifty-one (14%) developed local recurrence only, requiring surgery (four partial penectomies, three total penectomies). Six of these seven patients are alive and free of disease with a mean follow-up of 5.5 years. Nine of thirty eight (23%) patients with local control developed local necrosis. The treatment consisted of local excision (one patient), partial amputation (six patients) or total amputation (two patients). Partial urethral stenosis was noted in 17/38 (45%) of the patients. Foreskin sclerosis occurred in 3/38 (8%) uncircumcised patients. Interstitial irradiation for penile carcinoma provided effective local control rates, especially for T1-T2 patients (91%). Local failures could be treated successfully with surgery. Complications could be treated conservatively in most patients.
Local control with penile conservation was achieved in 67% of all patients and 75% of patients with T1-T2 disease.
Glansectomy: an alternative surgical treatment for Buschke-Lowenstein tumors of the penis.
Hatzichristou DG, Apostolidis A, Tzortzis V, Hatzimouratidis K, Ioannides E, Yannakoyorgos K.
Department of Urology, Aristotle University of Thessaloniki School of Medicine, Thessaloniki, Greece.
Urology 2001 May;57(5):966-9 Abstract quote
OBJECTIVES: To present the surgical excision of the glans penis (glansectomy) as an alternative surgical treatment to penectomy. Buschke-Lowenstein tumors of the penis include the entities described in published reports as verrucous carcinoma and giant condyloma acuminatum of the penis. Both types are well-differentiated tumors, typically confined to the glans penis, with distinctly rare metastatic activity.
METHODS: The study included 7 patients, 40 to 63 years of age, with exophytic, papillary lesions involving the glans penis. Biopsy led to the diagnosis of verrucous carcinoma in 4 patients and giant condyloma acuminatum in 3 patients. All patients reported normal erectile function. Because of the low malignant potential of the tumor and its confinement to the glans penis, a simple glansectomy was performed in all patients to preserve the maximal penile length and functional integrity of the corpora cavernosa.
RESULTS: The postoperative course was uncomplicated. With 18 to 65 months of follow-up, all patients were disease free. One patient required more aggressive treatment because of local recurrence of the tumor. All patients returned to normal sexual activity 1 month postoperatively. The only change during sexual activity, noted by two of the patients' partners, was vaginal pain, possibly due to the absence of the glans.
CONCLUSIONS: Glansectomy may be considered the treatment of choice in patients with Buschke-Lowenstein tumors of the penis, with more radical techniques reserved for second-line treatment.
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