Lichen sclerosus is frequently present in penile squamous cell carcinomas but is not always associated with oncogenic human papillomavirus

BACKGROUND: Penile squamous cell carcinoma (SCC) may occur on pre-existing lesions of lichen sclerosus (LS). However, the prevalence of histological changes of LS in penile SCC is not well established. Moreover, mucosal oncogenic human papillomaviruses (HPVs) are sometimes detected in penile SCC, but have not been systematically sought in LS-associated penile SCC. OBJECTIVES: To establish the prevalence of LS histological changes and of mucosal oncogenic HPV in a series of patients with penile SCC. METHODS: Consecutive cases of histologically proven penile SCC from a single university hospital over a 14-year period were retrospectively selected and reviewed. Histological signs of LS were systematically sought. HPV was detected by polymerase chain reaction (PCR) amplification of DNA from paraffin-embedded skin samples using general primers GP5+/GP6+ (allowing detection of mucosal HPV) and oncogenic type 16-, 18-, 31- and 33-specific primers. RESULTS: Eighteen cases of penile SCC were found. The mean +/- SD age of patients at diagnosis was 67.3 (14.5 years). In eight of 18 (44%) cases, SCC was associated with histological features of LS. Seventeen skin biopsy specimens of SCC (nine without and eight with LS histology) were subjected to PCR amplification for HPV. Mucosal HPV was detected in six of them (35%). Five of nine SCCs without histological features of LS were positive for mucosal HPV: three with HPV type 16 and two with only general primers. In contrast, all eight SCCs associated with LS were negative for oncogenic HPV types, although one was positive with general primers. CONCLUSIONS: Penile SCC seems to be frequently associated with LS histological changes. As with vulval SCC, we found that non-LS-associated penile SCC tended to be frequently associated with oncogenic HPV infection, whereas LS-associated penile SCC was not. Larger series are needed to confirm this association.     

Immunohistochemical staining of p16 in squamous cell carcinomas of the genital and extragenital area

Background and objectivesPositive immunostaining for the tumor suppressor protein p16 is associated with the presence of mucosal or αsubtypes of human papillomavirus (HPV) in cervical and genital squamous cell carcinoma (SCC). The aim of this study was to determine whether p16 immunostaining is also associated with mucosal HPV in extragenital SCC.Material and methodsParaffin sections of lesions located in the genital region (8 genital warts, 3 intraepidermal SCCs, and 7 invasive SCCs) and extragenital area (29 intraepidermal SCCs corresponding to Bowen disease and 10 invasive SCCs) were stained for p16 by immunohistochemistry. Mucosal HPV was detected by polymerase chain reaction (PCR).ResultsIn the genital area, p16 immunostaining was negative in genital warts and positive in all 3 intraepidermal SCCs and 2 invasive SCCs (29%). Mucosal HPV was detected in 6 genital warts and 2 intraepidermal SCCs (100% after exclusion of 3 lesions that could not be analyzed by PCR) and in the 2 invasive SCCs that were positive for p16. In the extragenital area, 19 intraepidermal SCCs (95%) and 2 invasive SCCs (20%) were immunopositive for p16. Mucosal HPV was detected in 4 intraepidermal SCCs (p16 immunopositive) and 1 invasive SCC (p16 immunonegative). In intraepidermal SCCs, p16 immunostaining facilitated the identification of dermal microinfiltration or invasion of normal skin appendages.ConclusionsAccording to our results, unlike in genital SCCs, p16 immunopositivity is independent of the presence of HPV in extragenital SCCs. Compared with intraepidermal SCCs, the absence of p16 protein in invasive SCCs in the extragenital area would indicate progression of the disease.     

Human papillomavirus type 26 infection causing multiple invasive squamous cell carcinomas of the fingernails in an AIDS patient under highly active antiretroviral therapy

Squamous cell carcinoma (SCC) of the nail unit is a rare disorder. An association with high-risk genital human papillomavirus (HPV) infection has been reported. We report a 28-year-old human immunodeficiency virus (HIV)-infected bisexual man who had multiple invasive SCC of the fingers, infected with the rare type HPV 26. Classification of HPV 26 as high- or intermediate-risk type has been uncertain, due to its rare presence in cervical cancer. Despite successful treatment with highly active antiretroviral therapy (HAART), the patient developed extensive hyperkeratotic nailbed proliferations of all fingers. Tumours were refractory to treatment and invaded into adjacent tissues. X-rays of the hands demonstrated bone invasion, necessitating amputation of distal phalanges of several fingers. Histologically, highly differentiated preinvasive and invasive verrucous SCCs were identified. Molecular DNA typing identified HPV 26 in the SCCs and in some premalignant lesions. By in situ hybridization HPV 26 DNA was detected in numerous tumour cells, indicating productive infection with high-level amplification of the viral genome. In the remaining proliferations, high-risk HPV type 58, cutaneous HPVs and a putative new HPV type were identified. HPV 26 infection appears to be causally involved in the development of SCC of the nail unit in this immunosuppressed patient. Timely evaluation of chronic verrucous nailbed tumours is recommended, especially in immunocompromised patients. Identification of HPV 26, besides known high-risk HPV types, may identify patients at risk for developing SCC of the nailbed and possibly at other locations.     

Detection of human papillomavirus DNA in squamous cell carcinomas of a patient with mycosis fungoides: report of a case

Human papillomaviruses (HPV) have been associated with squamous cell carcinomas (SCC) of the skin in both the immuno-competent and the immunocompromised individual. A paucity of literature, however, exists concerning die presence of HPV in SCCs from patients with mycosis fungoides (MF)-[cutaneous T-cell lymphoma (CTCL)]. We describe a case of multiple SCCs in which HPV DNA was detected over a 9-year period from a patient with MF. This patient with a long history of MF developed 7 small red scaly indurated lesions of sun and non-sun-exposed areas during a 9-year period (1981–1989). Histologic examination of all the lesions revealed that they were SCCs. The patient had no recorded history of arsenic exposure. To investigate the possible role of HPV as a co-carcinogen, we tested the 7 cases of SCC for HPV. Polymerase chain reaction (PCR) was performed on formalin-fixed tissue sections using HPV L1 consensus sequence primers. Four of the 7 SCCs were positive for HPV DNA. These results suggest a possible role for HPV as a co-carcinogen in the development of SCCs in this patient.     

Fluorescence diagnosis in actinic keratosis and squamous cell carcinoma

Background: As different tissue types have distinct capabilities to accumulate protoporphyrin IX, fluorescence diagnosis with aminolevulinic acid‐induced porphyrins (FDAP) could be used to discriminate between different types of tissue. Previous results demonstrated higher fluorescence ratios in squamous cell carcinoma (SCC) compared with actinic keratoses (AKs). Objectives: The lesional : non‐lesional fluorescence ratio of AKs was compared with the ratio of SCC. Other factors influencing macroscopic fluorescence were also assessed, including stratum corneum thickness, which has been demonstrated to account for heterogeneous fluorescence in psoriasis and in AKs. Methods: After 1 week of keratolytic pretreatment, FDAP was performed in 13 patients with 36 lesions suspected for AK or SCC. Biopsies were taken for histopathological diagnosis and measurement of stratum corneum thickness. Results: No significant differences were found in the fluorescence ratio (lesional : non‐lesional skin) between AKs and SCCs, although macroscopic fluorescence was significantly higher in Bowen's disease and micro‐invasive SCCs. Conclusions: There could be a potential applicability of FDAP to differentiate premalignant lesions with a tendency to progress into SCC and squamous cutaneous lesions already progressing into early invasive cancer from other squamous cutaneous (pre)malignancies. The amount of hyperkeratosis, invasiveness and degree of differentiation seem to be responsible for variations in fluorescence intensity.     

Cutaneous manifestations of dabrafenib (GSK2118436): a selective inhibitor of mutant BRAF in patients with metastatic melanoma

Background Inhibitors of mutant BRAF are emerging as standard of care in patients with metastatic melanoma carrying relevant oncogenic mutations. Cutaneous reactions are frequent and significant. We conducted a systematic prospective dermatological review of all patients enrolled at a single institution in the phase I/II clinical trial of the mutant BRAF inhibitor dabrafenib (GSK2118436). Objectives To identify the cutaneous manifestations of the BRAF inhibitor dabrafenib; to form diagnostic criteria to standardize the diagnosis of verrucal keratotic squamoproliferative lesions; and to bring awareness to the medical community of the importance of dermatological assessment of patients taking dabrafenib. Methods Patients enrolled in the phase I/II trial (n = 43) were monitored for the development of new skin lesions. Each new lesion was photographed, a clinical diagnosis recorded and, where appropriate, a biopsy taken. Human papillomavirus (HPV) and p16 immunohistochemistry analyses were performed. Results The most frequently observed lesions were verrucal keratotic squamoproliferative lesions (49%), Grover’s disease (27%) and reactive hyperkeratotic lesions on the soles, at points of friction (22%). Eighteen squamous cell carcinomas (SCCs) occurred in 20% of patients. Most SCCs appeared between weeks 6 and 24 following commencement of therapy on both sun‐damaged and nonsun‐damaged skin. All SCCs were well differentiated, five were of the keratoacanthoma type, and two were SCC in situ. Other lesions observed included seborrhoeic keratoses, epidermal cysts, acneiform eruptions, hair loss and changes in hair structure. HPV was negative in 15 of the 16 tissues studied and p16 expression was higher in SCCs compared with verrucal keratoses. Conclusions Administration of the mutant BRAF inhibitor dabrafenib is associated with induction of keratinocytic proliferation, which in some cases develops features of low‐grade malignancy. Highly oncogenic HPV infection is unlikely to be a contributor to the formation of SCCs or verrucal keratoses.     

Human papillomavirus in cutaneous squamous cell carcinoma and cervix of a patient with psoriasis and extensive ultraviolet radiation exposure

"High-risk" human papillomaviruses (HPVs) are associated with intraepithelial neoplasia and cancer of the uterine cervix. HPV has also been found in nonmelanoma skin cancer (NMSC), especially in squamous cell carcinomas (SCCs) of immunosuppressed patients. Recently, lesions of psoriasis have been shown to harbor HPV, and patients with psoriasis often have a history of extensive therapy with ultraviolet radiation (UVR). UVR is the major known risk factor in the occurrence of NMSC, in which HPV may be a cofactor for SCC. We report an otherwise healthy, nonimmunosuppressed patient with psoriasis who had a history of extensive exposure to UVR and experienced multiple SCCs on UV-exposed body sites. By the polymerase chain reaction method, we detected HPV in 5 of 9 SCCs. Automated sequencing showed HPV types 12 and 17. Only 1 of 3 normal skin specimens was HPV positive (HPV type 17). This positive specimen was from UV-exposed skin; one of the two HPV-negative, normal skin specimens was located on a body site not exposed to sun. In addition, HPV type 62 was found in a brush specimen of the uterine cervix. This case report suggests an association between psoriasis, HPV infection, and UVR exposure, in onset of SCC.     

Multiple human papillomavirus-16 associated digital squamous-cell carcinomas in an immunocompetent woman with prior human papillomavirus-related genital carcinoma

High-risk subtype human papillomavirus (HPV) infection, which is known to contribute to the oncogenesis of anogenital squamous-cell carcinoma (SCC), is detected in the majority of digital SCCs. Evidence suggests a genital-digital route of transmission of high-risk HPV, and most HPV-related digital SCCs occur near the nail unit in immunocompetent adults. As early HPV-related SCC commonly appears as a verrucous periungual papule, a biopsy should be considered if such a lesion persists or occurs in an individual who is likely to inoculate their digits with high-risk HPV from digital-genital contact with themselves or sexual partners. We present a 60-year-old woman, who has a personal history of vulvar and cervical SCC and an appreciable disease burden from SCCs that involved five digits of her hands.     

皮肤鳞状细胞癌300例临床及病理回顾分析

目的 探讨皮肤鳞状细胞癌(SCC)的临床及病理特征.方法 回顾性分析总结2000年1月1日-2009年12月31日郑州大学第一附属医院经病理确诊的皮肤SCC首发病例的临床资料.结果 该院10年共确诊皮肤SCC300例,男女比例约为1.86:1.50岁及以上者223例(74.33%),暴露部位170例(56.67%).临...     

The role of p53 codon 72 and human papilloma virus status of cutaneous squamous cell carcinoma in the Swedish population

The arginine variant of the p53 codon 72 polymorphism as well as anogenital and epidermodysplasia verruciformis (EV) types of human papilloma virus (HPV) are suggested to confer increased risk for developing cutaneous squamous cell carcinoma (SCC). In this pilot study, we analysed the p53 codon 72 genotype distribution in 106 microdissected samples from normal and tumour tissues of 53 cases of cutaneous SCC and 96 controls from Sweden. Both normal and tumour samples from cases of SCC were screened for anogenital and EV HPV. The p53Arg allele was not associated with the development of cutaneous SCC. Anogenital HPV (44%) was more prevalent than EV HPV (12%). Data also indicate that anogenital HPV is more common in tumour samples, but HPV infection was not identified as a significant risk factor for developing SCC. The presence of anogenital HPV, but not EV HPV might be a risk factor for development of cutaneous SCC.     

Lymphatic mapping and sentinel lymphonodectomy in recurrent cutaneous squamous cell carcinomas

There are subsets of cutaneous squamous cell carcinoma (SCC), including recurrent tumours, that have a high-risk for both local recurrence and metastasis. Since the presence of regional lymph node metastases carries a poor prognosis, the early evaluation of the nodal status is crucial for staging and treatment planning. Recent trials have shown that the lymphatic mapping (LM) and sentinel lymphonodectomy (SLNE) may be successfully employed to screen nodal basins in patients with high-risk cutaneous SCCs at clinical stage N0. We report our experience with this procedure in five selected patients affected with recurrent cutaneous SCCs. A metastatic sentinel lymph node (SLN) was found in 1 of the 5 cases. No false negative result was observed. SLNE is a feasible and minimally invasive staging procedure in patients with high-risk cutaneous SCCs. It may select patients with clinically occult metastases in the regional nodal basins, who can be submitted to therapeutic lymph node dissection (LND), avoiding the morbidity of a prophylactic LND in patients without metastases in SLNs.     

Widespread cutaneous carcinomas associated with human papillomaviruses 5, 14 and 20 after introduction of methotrexate in two long-term PUVA-treated patients

BACKGROUND: PUVA treatment for patients with severe psoriasis has been demonstrated to be highly effective. However, an increased risk of nonmelanoma and melanoma skin cancers has been reported. It is generally accepted that the risk of squamous-cell carcinoma (SCC) is significantly increased in patients with long-term PUVA therapy. The role of methotrexate (MTX) and infection with oncogenic human papillomaviruses which may act as cocarcinogens is poorly documented. CASE REPORTS: Two cases of multiple SCCs associated with numerous PUVA keratoses and PUVA freckles after long-term PUVA therapy and subsequent treatment with MTX are presented. In 1 case, the tumor progressed to metastatic SCC. Tumors and scrapings of psoriatic skin lesions were analyzed for the presence of oncogenic human papillomavirus (HPV) genotypes. The genotype of HPV-5, -14 and -20 was detected in scrapings and skin tumors using PCR amplification. CONCLUSION: These observations support the concept that long-term PUVA treatment is carcinogenic and rise questions concerning an additional influence of MTX in the development and progression of skin cancer. The risk of metastatic SCC seems to be underestimated in high-dose PUVA-treated patients due to longer latency for developing metastases and the small number of studies with long-term follow-up. Treatment with MTX should be considered cautiously in patients previously exposed to high doses of PUVA. The presence of oncogenic HPVs in carcinomas and psoriatic skin lesions detected only with the highly sensitive nested PCR method is not necessarily a proof of their implication in skin carcinogenesis.     

Cutaneous squamous cell carcinoma: a comprehensive clinicopathologic classification--part two

Cutaneous squamous cell carcinoma (SCC) includes many subtypes with widely varying clinical behaviors, ranging from indolent to aggressive tumors with significant metastatic potential. However, the tendency for pathologists and clinicians alike is to refer to all squamoid neoplasms as generic SCC. No definitive, comprehensive clinicopathological system dividing cutaneous SCCs into categories based upon their aggressiveness has yet been promulgated. Therefore, we have proposed the following based upon the malignant potential of SCC variants, separating them into categories of low (< or = 2% metastatic rate), intermediate (3-10%), high (greater than 10%), and indeterminate behavior. Low-risk SCCs include SCC arising in actinic keratosis, HPV-associated SCC, tricholemmal carcinoma, and spindle cell SCC (unassociated with radiation). Intermediate-risk SCCs include adenoid (acantholytic) SCC, intraepidermal epithelioma with invasion, and lymphoepithelioma-like carcinoma of the skin. High-risk subtypes include de novo SCC, SCC arising in association with predisposing factors (radiation, burn scars, and immunosuppression), invasive Bowen's disease, adenosquamous carcinoma, and malignant proliferating pilar tumors. The indeterminate category includes signet ring cell SCC, follicular SCC, papillary SCC, SCC arising in adnexal cysts, squamoid eccrine ductal carcinoma, and clear-cell SCC. Subclassification of SCC into these risk-based categories, along with enumeration of other factors including tumor size, differentiation, depth of invasion, and perineural invasion will provide prognostically relevant information and facilitate the most optimal treatment for patients.     

Cutaneous squamous cell carcinoma: a comprehensive clinicopathologic classification. Part one

Cutaneous squamous cell carcinoma (SCC) includes many subtypes with widely varying clinical behaviors, ranging from indolent to aggressive tumors with significant metastatic potential. However, the tendency for pathologists and clinicians alike is to refer to all squamoid neoplasms as generic SCC. No definitive, comprehensive clinicopathological system dividing cutaneous SCCs into categories based upon their aggressiveness has yet been promulgated. Therefore, we have proposed the following based upon the malignant potential of SCC variants, separating them into categories of low (< or = 2% metastatic rate), intermediate (3-10%), high (greater than 10%), and indeterminate behavior. Low-risk SCCs include SCC arising in actinic keratosis, HPV-associated SCC, tricholemmal carcinoma, and spindle cell SCC (unassociated with radiation). Intermediate-risk SCCs include adenoid (acantholytic) SCC, intraepidermal epithelioma with invasion, and lymphoepithelioma-like carcinoma of the skin. High-risk subtypes include de novo SCC, SCC arising in association with predisposing factors (radiation, burn scars, and immunosuppression), invasive Bowen's disease, adenosquamous carcinoma, and malignant proliferating pilar tumors. The indeterminate category includes signet ring cell SCC, follicular SCC, papillary SCC, SCC arising in adnexal cysts, squamoid eccrine ductal carcinoma, and clear-cell SCC. Subclassification of SCC into these risk-based categories, along with enumeration of other factors including tumor size, differentiation, depth of invasion, and perineural invasion will provide prognostically relevant information and facilitate the most optimal treatment for patients.     

Combined sentinel lymphadenectomy and mohs micrographic surgery for high-risk cutaneous squamous cell carcinoma

BACKGROUND: There are subgroups of cutaneous squamous cell carcinoma (SCC) that have a higher risk for both regional and distant metastasis. When cutaneous SCC does metastasize, it typically spreads first to local nodal groups. Sentinel lymph node (SLN) localization has been successfully used to evaluate nodal metastasis in breast carcinoma, melanoma, and other select tumors. It may also be useful in certain high-risk cutaneous SCCs. Currently, Mohs micrographic surgery is the treatment of choice for these tumors. METHODS: A patient presented with a high-risk recurrent SCC on the forehead. The regional nodal groups were clinically negative and radiographically negative by computed tomographic scan. Sentinel lymphadenectomy was performed by means of technetium 99m-radiolabeled sulfur colloid. The main tumor was resected with Mohs micrographic surgery. RESULTS: A left preauricular SLN was localized by lymphoscintigraphy. The SLN was located intraoperatively by means of a gamma probe and excised. Subsequent pathologic evaluation of the SLN was negative for evidence of metastatic SCC by light microscopy with hematoxylin and eosin, and with immunohistochemical stains for cytokeratins AE1 and AE3. The day after SLN excision, the tumor was removed via Mohs micrographic surgery with clear surgical margins after a total of 8 stages. Aggressive subclinical spread by both subcutaneous "skating" and perineural invasion was noted. CONCLUSION: The combination of Mohs micrographic surgery and sentinel lymphadenectomy is feasible and has theoretical utility in the management of a subset of cutaneous SCCs at high risk for metastasis. The ability of sentinel lymphadenectomy to identify regionally metastatic cutaneous SCC as well as the additive benefit of SLN and Mohs micrographic extirpation in the treatment of high-risk cutaneous SCC remain to be further clarified.     

皮肤鳞状细胞癌和基底细胞癌中细胞凋亡及c-fos、BNIP1表达

目的观察皮肤鳞状细胞癌(鳞癌)和基底细胞癌(基癌)中细胞凋亡及其与c-fos、BNIP1表达的关系。方法应用原位末端标记和原位杂交技术检测48例皮肤鳞癌和41例基癌标本中细胞凋亡及C-fos、BNIP1 mRNA表达。结果鳞癌中凋亡指数(AI)、c-fos mRNA表达明显高于基癌(P＜0．01),但BNIP1 mRNA表达在二者间的差异无显著性(P＞0．05)。AI在高分化鳞癌中明显增多(P＜0．05),但C-fos表达以低分化鳞癌更为明显(P＜0．05)。鳞癌中AI与c-fos、BNIP1表达呈显著正相关(P＜0．05)。结论鱗癌中细胞凋亡增多与c-fos表达上调相关,BNIP1在鳞癌和基癌中可能起促凋亡作用。     

Expression and glycosylation of MUC1 in epidermolysis bullosa-associated and sporadic cutaneous squamous cell carcinomas

BACKGROUND: Cutaneous squamous cell carcinoma (SCC) is particularly problematic in certain patient groups, including patients with dystrophic or junctional epidermolysis bullosa (DEB/JEB). Theoretically, vaccination against a cell surface antigen which is expressed on this type of tumour could prevent SCC development, as well as treat primary and metastatic disease in this patient group. Preliminary studies have suggested that MUC1, a transmembrane glycoprotein, is overexpressed in sporadic cutaneous SCCs, and MUC1 has been used with some success as a target antigen for vaccine development in breast cancer, where it is expressed on > 50% of neoplastic cells in approximately 50-80% of tumours. Furthermore, aberrant glycosylation of MUC1 has been detected in this and other cancer types; however, the glycosylation status of MUC1 in cutaneous SCC is not known. OBJECTIVES: To investigate the expression and glycosylation status of MUC1 in SCCs arising in patients with DEB and JEB, and for comparison in sporadic SCCs and sporadic Bowen's disease. METHODS: Immunohistochemical analysis of MUC1 in 30 SCCs from subjects with DEB/JEB, 55 sporadic SCCs and 30 sporadic lesions of Bowen's disease was carried out using four separate monoclonal antibodies which recognize different isoforms of MUC1. RESULTS: Expression of MUC1 was detected in 100% of SCCs arising in patients with DEB and JEB; > 50% of neoplastic cells stained positive for MUC1 in 57% of DEB/JEB SCCs, with over 95% of tumour cells immunopositive in 33% of cases. MUC1 expression was also observed in 95% of sporadic SCCs and 97% of Bowen's disease, with 36% of sporadic SCCs immunopositive for MUC1 in > 50% of tumour cells. Investigation of the glycosylation status showed that MUC1 was predominantly hyperglycosylated in the DEB/JEB and sporadic tumours. CONCLUSIONS: The results demonstrate that a significant proportion of DEB/JEB and sporadic SCCs express MUC1 in > 50% of tumour cells. Therefore, MUC1 may be a suitable candidate antigen against which to develop a tumour vaccine for these patient groups.     

周期素A在皮肤鳞状细胞癌与角化棘皮瘤中的检测

目的通过检测周期素(cyc lin)A在皮肤鳞状细胞癌(SCC)和角化棘皮瘤(KA)中的分布,探讨两者之间的关系。方法采用免疫组化技术检测12例KA和20例SCC皮损中cyc lin A蛋白。结果cyc lin A阳性细胞在KA中主要位于肿瘤的周边部,而在SCC中,呈弥漫性分布;cyc lin A在KA中的平均阳性率(13.2%)与高分化SCC(15.5%)差异无显著性(P>0.05),但与中、低分化SCC(23.4%,33.6%)差异有显著性(P<0.05)。结论cyc lin A在KA与SCC中的分布特点进一步说明了两者的异同,KA是否是SCC的分型尚需进一步探讨;cyc lin A在KA及各型SCC中的阳性率的不同说明cyc lin A可以作为评价皮肤肿瘤增殖程度的一个分子生物学指标。     

Human papillomavirus-associated increase in p16INK4A expression in penile lichen sclerosus and squamous cell carcinoma.

BACKGROUND: Human papillomaviruses (HPVs) are sexually transmitted human carcinogens that may play a role in the oncogenesis of penile cancer. OBJECTIVES: To investigate the role of HPV infection and expression of the tumour suppressor protein p16INK4A in the pathogenesis of penile cancer. METHODS: By means of polymerase chain reaction amplification and reverse hybridization line probe assay to detect HPV infection, and immunohistochemical staining for p16INK4A and Ki67, we analysed 26 penile squamous cell carcinomas (SCCs) and 20 independent penile lichen sclerosus (LS) lesions from 46 patients. RESULTS: HPV DNA was found in 54% of penile SCCs and 33% of penile LS cases in single and multiple infections. High-risk HPV 16 was the predominant HPV type detected. No relationship between Ki67 expression and HPV infection was observed. Strong immunostaining for p16INK4A correlated with HPV 16/18 infection in both penile LS and penile SCC. In our penile SCC series the cancer margins were also associated with penile LS in 13 of 26 lesions, and HPV was detected in seven of the 13 SCC cases associated with LS and in six of the 11 SCC lesions not involving LS. CONCLUSIONS: Our study shows a high prevalence of HPV 16 and p16INK4A expression in penile lesions, consistent with an active role for HPV in interfering with the retinoblastoma pathway. High-risk HPV infection could be involved in the tumorigenic process in 50% of penile cancers, and the use of prophylactic HPV vaccines has the potential to prevent these cancers.     

Follicular squamous cell carcinoma of the skin: a poorly recognized neoplasm arising from the wall of hair follicles

BACKGROUND: In the last decades, a number of clinicopathologic subtypes of squamous cell carcinoma (SCC) of the skin, ranging from highly aggressive tumors with a tendency to recur and metastasize to neoplasms with a favorable prognosis, have been described. SCCs arising from the wall of hair follicles have been briefly mentioned by some authors but never reported in a series. METHODS: Cases of SCC arising from the wall of hair follicles were collected from the files of two large German Centers for Dermatopathology and analyzed clinicopathologically and immunohistochemically. RESULTS: Sixteen cases of SCC developing in hair follicles were found among more than 7000 cases of cutaneous SCC reviewed. In most cases, tumors arose on sun-damaged skin of the face of elderly persons. There was a male predominance (11/5). The most common clinical diagnosis was basal cell carcinoma (BCC). Microscopically, tumors developed in the upper part of hair follicles without or with focal involvement of the overlying epidermis at the border with the involved follicle. Immunohistochemically, tumors were positive for cytokeratin and negative for a battery of immunomarkers, including antibodies against the most common carcinogenic human papillomaviruses (HPV) of the skin. Most tumors were excised by simple excision. In two cases, a recurrence was noted after incomplete excision. No further recurrences or metastasis have been noted after a follow-up period ranging from 11 months to 12 years. CONCLUSION: SCC of the hair follicle represents a poorly recognized but distinctive subset of SCC of the skin that should be considered in the differential diagnosis of other cutaneous epithelial tumors. The term follicular SCC (FSCC) is proposed for this neoplasm.