Primary Invasive Squamous Cell Carcinoma Research Articles

Limited impact of COVID-19-related diagnostic delay on cutaneous melanoma and squamous cell carcinoma tumour characteristics: a nationwide pathology registry analysis.

BackgroundThe COVID‐19 pandemic reduced the number of skin cancer diagnoses, potentially causing a progression to unfavourable tumour stages.ObjectivesTo identify the impact of delayed diagnostics on primary invasive melanoma and cutaneous squamous cell carcinoma (cSCC) by comparing tumour (pT) stage, Breslow thickness and invasion depth from before to after the first and second lockdown periods.MethodsIn this population‐based cohort study, histopathology reports registered between 1 January 2018 and 22 July 2021 were obtained from the nationwide histopathology registry in the Netherlands. The Breslow thickness of melanomas, invasion depth of cSCCs, and pT stage for both tumour types were compared across five time periods: (i) pre‐COVID, (ii) first lockdown, (iii) between first and second lockdowns, (iv) second lockdown and (v) after second lockdown. Breslow thickness was compared using an independent t‐test. pT‐stage groups were compared using a χ2‐test. Outcomes were corrected for multiple testing using the false discovery rate.ResultsIn total, 20 434 primary invasive melanomas and 68 832 cSCCs were included in this study. The mean primary melanoma Breslow thickness of the prepandemic era (period i) and the following time periods (ii–v) showed no significant difference. A small shift was found towards unfavourable pT stages during the first lockdown compared with the pre‐COVID period: pT1 52·3% vs. 58·6%, pT2 18·9% vs. 17·8%, pT3 13·2% vs. 11·0%, pT4 9·1% vs. 7·3% (P = 0·001). No relevant changes were seen in subsequent periods. No significant change in pT stage distribution was observed between the pre‐COVID (i) and COVID‐affected periods (ii–v) for cSCCs.ConclusionsTo date, the diagnostic delay caused by COVID‐19 has not resulted in relatively more unfavourable primary tumour characteristics of melanoma or cSCC. Follow‐up studies in the coming years are needed to identify a potential impact on staging distribution and survival in the long term.

The expression of ribonuclear protein IMP3 in laryngeal carcinogenesis

ObjectiveThe aim of the study was to investigate the expression of ribonuclear protein IMP3 in laryngeal carcinogenesis, together with other biomarkers of carcinogenesis (Ki-67, p53 and cyclin D1), and to evaluate their predictive values. MethodsThe study included 153 patients divided into three groups: 68 operated for primary invasive laryngeal squamous cell carcinoma (LSCC); 41 with precancerous lesions of atypical and abnormal hyperplasia; 44 with hyperplastic laryngeal nodule without atypia. Tissue microarray technique was used for immunohistochemical analysis. ResultsAll markers showed statistically significant differences between the three groups. The percentage of IMP3 positive cells is statistically significantly higher in LSCC group in comparison to precancerosis and control group. The percentage of Ki-67 positive cells is statistically significantly higher in LSCC group in comparison to precancerosis and control group. The percentage of p53 positive cells in LSCC group is statistically significantly higher than the control group and higher, but not statistically significant, than the precancerosis group. The percentage of cyclin D1 positive cells is statistically significantly higher in LSCC group than in precancerosis group and higher, but not statistically significant, than in the control group. All analyzed markers have good predictive values (AUC > 0.6), but the percentage of IMP3 positive cells is the only statistically significant marker in predicting whether the patient has LSCC or not. ConclusionExpression of Ki-67 and pronouncedly IMP3 generally follow the same pattern where control and precancerosis are similar and LSCC significantly differs, as opposed to p53 and cyclin D1. IMP3 expression increase possibly has an important diagnostic, therapeutic (in terms of the need for additional therapy after surgery) and prognostic value. Further studies on the exact molecular mechanisms behind it are, of course, needed.

Liquid biopsy of HPV DNA in cervical cancer

BackgroundA blood test to serve as a tumor marker for cervical cancer would be useful to clinicians to guide treatment and provide an early signal for recurrence. The development of droplet digital PCR has enabled the detection of HPV DNA in patient serum, providing a potential marker for cervical cancer. ObjectivesTo report on a blood-based test for HPV-specific E7 and L1 genes, which may serve as a tumor marker to guide treatment and detect early recurrence in cervical cancer. Study designPre-treatment plasma samples were investigated from 138 Hong Kong Chinese women with primary invasive squamous cell carcinoma and adenocarcinoma of the cervix with tumor samples expressing HPV16 or HPV18. Two genes specific to the human papillomavirus, E7 and L1, were measured in cell free DNA (cfDNA) extracted from plasma using droplet digital PCR. Analysis of detectable E7 and L1 levels was performed to investigate the potential of liquid biopsy of E7 and L1 as a clinically useful molecular biomarker. ResultsThe majority of patients had HPV16 (71.7%), squamous cell carcinoma (78.3%) and stage IB-II disease (82.6%). HPV E7 and L1 sequences were detected in plasma cfDNA from 61.6% (85/138) of patients. Patients with high viral load (defined as ≥20 E7 or L1 copies per 20 μL reaction volume) had increased risk of recurrence and death at 5 years on univariate analysis but not multivariate analysis. ConclusionsHPV DNA can be quantitatively detected with the use of cfDNA. This has the potential to provide a clinically useful tumor marker for patients with cervical cancer that can aid in post-treatment surveillance and estimating the risk of disease relapse.

Analysis of full coding sequence of the TP53 gene in invasive vulvar cancers: Implications for therapy

ObjectiveThis study evaluates the frequency and type of TP53 gene mutations and HPV status in 72 consecutively diagnosed primary invasive vulvar squamous cell carcinomas (SCC) during the past 5years. MethodsDNA of formalin-fixed and paraffin embedded tumour tissue was analysed for 32 HPV subtypes and the full coding sequence of the TP53 gene, and correlated with results of p53 immunohistochemistry. Results13/72 (18%) cancers were HPV-induced squamous cell carcinomas, of which 1/13 (8%) carcinoma harboured a somatic TP53 mutation. Among the 59/72 (82%) HPV-negative cancers, 59/72 (82%) SCC were HPV-negative with wild-type gene in 14/59 (24%) SCC and somatic TP53 mutations in 45/59 (76%) SCC. 28/45 (62%) SCC carried one (n=20) or two (n=8) missense mutations. 11/45 (24%) carcinomas showed a single disruptive mutation (3× frame shift, 7× stop codon, 1× deletion), 3/45 SCC a splice site mutation. 3/45 (7%) carcinomas had 2 or 3 different mutations. 18 different “hot spot” mutations were observed in 22/45 cancers (49%; 5× R273, 3× R282; 2× each Y220, R278, R248). Immunohistochemical p53 over expression was identified in most SCC with missense mutations, but not in SCC with disruptive TP53 mutations or TP53 wild-type. 14/45 (31%) patients with TP53 mutated SCC died of disease within 12months (range 2–24months) versus 0/13 patients with HPV-induced carcinomas and 0/14 patients with HPV-negative, TP53 wild-type carcinomas. Conclusion80% of primary invasive vulvar SCC were HPV-negative carcinomas with a high frequency of disruptive mutations and “hot spot” TP53 gene mutations, which have been linked to chemo- and radioresistance. The death rate of patients with p53 mutated vulvar cancers was 31%. Immunohistochemical p53 over expression could not reliably identify SCC with TP53 gene mutation. Pharmacological therapies targeting mutant p53 will be promising strategies for personalized therapy in patients with TP53 mutated vulvar cancers.

The Added Value of Pathology Review in Vulvar Cancer: Results From a Population-based Cohort Study.

We conducted a population-based patterns of care study of vulvar carcinoma. This paper describes the changes in reporting based on pathology review. This is a retrospective population-based cohort study. We obtained all pathology records available from the provincial cancer registry for primary invasive squamous cell carcinoma of the vulva diagnosed between 1998 and 2007. Pathology reviews were conducted centrally by a group of gynecologic pathologists and were identified during abstraction. Corresponding original reports were matched to pathology review reports based on accession numbers. We compared the reported value for presence/absence of invasion, grade, depth, thickness, size, lymphovascular space invasion, peripheral margin status, and deep margin status in the original and review report. A total of 1011 vulvar resection reports were identified. From these, we identified 316 pairs of original/review reports. Missing data were common but improved in the reviews. In total, 55 (17%) reports had at least 1 change from the original to the review based on presence of invasion, depth, lymphovascular space invasion, or margin. When we included reports where a variable was missing in the original but then completed in the review, there were clinically relevant changes in 210 reports (66%). Vulvar carcinoma is a rare diagnosis and pathology reviews resulted in potentially important clinical changes in a significant proportion of cases. Referral pathologists play an important role in contributing to high-quality clinical decisions.

Surgical Margins Identified As a Major Area of Uncertainty in the Management of High-Risk Cutaneous Squamous Cell Carcinoma (cSCC)

The Scottish Intercollegiate Guidelines Network (SIGN) has developed guidelines for primary invasive cutaneous squamous cell carcinoma (cSCC). SIGN 140 Key questions included: (i) Which features, or combination of features, best identify high-risk cSCC? (ii) What are the most effective interventions for management of patients with cSCC? (iii) What is the optimum surgical margin and what histological clearance margins are acceptable? The evidence base was synthesised in accordance with SIGN methodology (SIGN 50), which complies with the internationally recognised AGREE criteria for guideline development based on a systematic review of the published literature. Databases searched included Medline, Embase, Cinahl and the Cochrane Library. Systematic searches were supplemented by material (mostly historic) identified by members of the development group. Initial searches identified 5712 hits, from which 492 abstracts were screened and 164 studies read in full and critically appraised before 91 were accepted as evidence on which to base recommendations. A systematic review and pooled analysis of observational studies was used as a basis for treatment recommendations. This process identified those clinical and histopathological features where there is robust evidence for association with poor outcomes (local recurrence, metastasis, disease-related death) allowing recognition of cSCC where referral to a regional skin cancer MDT meeting is appropriate. A minimum dataset highlighting these features would facilitate automatic referral and has been developed. Four key features; diameter, depth, differentiation and perineural invasion were identified onmultivariate analysis as associated with at least 2 of the 3 poor outcomes. Additional independent high-risk features identified were desmoplastic subtype, location on ear and immunosuppression. Recommendations and good practice points for surgical margins, Mohs Micrographic Surgery (MMS), radiotherapy and curettage have been developed, but the evidence base for surgical margins and for use of adjuvant radiotherapywas limited, with very little data relating surgical or histologicalmargins to outcomes. In retrospective analysis most incomplete excisions show persistence at the deep margin suggesting future studies should focus on deep as well as radial margins. Furthermore, the role

Expression of Human Kallikrein Protein and mRNA in Maxillofacial Cysts and Tumors

The Scottish Intercollegiate Guidelines Network (SIGN) has developed guidelines for primary invasive cutaneous squamous cell carcinoma (cSCC). SIGN 140 Key questions included: (i) Which features, or combination of features, best identify high-risk cSCC? (ii) What are the most effective interventions for management of patients with cSCC? (iii) What is the optimum surgical margin and what histological clearance margins are acceptable? The evidence base was synthesised in accordance with SIGN methodology (SIGN 50), which complies with the internationally recognised AGREE criteria for guideline development based on a systematic review of the published literature. Databases searched included Medline, Embase, Cinahl and the Cochrane Library. Systematic searches were supplemented by material (mostly historic) identified by members of the development group. Initial searches identified 5712 hits, from which 492 abstracts were screened and 164 studies read in full and critically appraised before 91 were accepted as evidence on which to base recommendations. A systematic review and pooled analysis of observational studies was used as a basis for treatment recommendations. This process identified those clinical and histopathological features where there is robust evidence for association with poor outcomes (local recurrence, metastasis, disease-related death) allowing recognition of cSCC where referral to a regional skin cancer MDT meeting is appropriate. A minimum dataset highlighting these features would facilitate automatic referral and has been developed. Four key features; diameter, depth, differentiation and perineural invasion were identified onmultivariate analysis as associated with at least 2 of the 3 poor outcomes. Additional independent high-risk features identified were desmoplastic subtype, location on ear and immunosuppression. Recommendations and good practice points for surgical margins, Mohs Micrographic Surgery (MMS), radiotherapy and curettage have been developed, but the evidence base for surgical margins and for use of adjuvant radiotherapywas limited, with very little data relating surgical or histologicalmargins to outcomes. In retrospective analysis most incomplete excisions show persistence at the deep margin suggesting future studies should focus on deep as well as radial margins. Furthermore, the role

Primary Invasive Squamous Cell Carcinoma of the Nipple.

Squamous cell carcinoma is one of the most common cutaneous cancers; however, primary squamous cell carcinoma of the nipple is extremely rare. Among the few reported cases, the majority have occurred in older women with rare cases seen in younger women and male patients. Our patient presented with an exophytic mass of the right nipple while pregnant. A superficial biopsy was reviewed at an outside institution and then at our institution and diagnosed as squamous papilloma and then as hyperkeratosis of the nipple, respectively. The subsequent excisional biopsy revealed multiple nests of tumor cells extending into the dermis with associated chronic inflammatory infiltrate, and the lesion was diagnosed as a primary invasive squamous cell carcinoma of the nipple. Following that, a wide local excision of the excision site and sampling of the regional lymph nodes were negative for carcinoma. Due to the rarity of this diagnosis, it is not known whether prognosis and response to therapy differ from cutaneous squamous cell carcinoma at other sites. Therefore, risk stratification and therapy have been based on those for cutaneous squamous cell carcinoma.

The Impact of Comorbidity on Treatment (Chemoradiation and Laryngectomy) of Advanced, Nondistant Metastatic Laryngeal Cancer

To investigate whether patients treated with laryngectomy had less comorbidity than those treated with chemoradiation, which could help explain the improved survival for the laryngectomy cohorts in recent studies. Observational cross-sectional study. Patients receiving diagnoses of primary invasive advanced squamous cell carcinoma of the larynx between 2003 and 2008 were selected from the National Cancer Database, which collects information from more than 1400 facilities accredited by the American College of Surgeons' Commission on Cancer. Patient-level independent variables included age at diagnosis, sex, diagnosis year, race/ethnicity, primary payer status, and zip code-level education. Primary treatment information. The association between treatment and patient clinical, sociodemographic, and facility-level and zip code-level socioeconomic status variables were analyzed using univariate statistics and multivariate models. Charlson Deyo Comorbidity and The Washington University Head and Neck Comorbidity Index scores were calculated from the hospital face sheet. The study demonstrated that receipt of treatment (chemoradiation vs total laryngectomy) was significantly associated with comorbidity. Treatment was not significantly associated with insurance status, race/ethnicity, or age. Patients with comorbidity were less likely to receive chemoradiation than subtotal or total laryngectomy, with a risk ratio (RR) of 0.84 (95% CI, 0.81-0.87) for patients with 1 or more comorbidities compared with those without any comorbidity, after controlling for factors such as tumor stage, age, race/ethnicity, insurance, and socioeconomic status. Patients were also less likely to receive chemoradiation than total laryngectomy if they had stage IV disease (RR, 0.81; 95% CI, 0.79-0.83) and if they had been diagnosed at a teaching or research institution (RR, 0.80; 95% CI, 0.77-0.84). Patients were more likely to receive chemoradiation if they were diagnosed after 2003 (RR, 1.37; 95% CI, 1.30-1.45) or if they lived in a zip code with a high percentage of high school graduates (RR, 1.1; 95% CI, 1.05-1.15). This is the first study, to our knowledge, that demonstrates that patients with advanced laryngeal cancer with 1 or more comorbidities are more likely to receive surgery than chemoradiation compared with patients without any comorbidity, independent of numerous clinical and nonclinical variables among a large national cohort. A limitation of this study is the use of comorbidity data from the National Cancer Database, which gathers its information from hospital discharge face sheets. We recognize that the National Cancer Database may be an imperfect system for the collection of comorbidity data and encourage discussion on different methods to improve the system, including incorporating comorbidity data from the Surveillance, Epidemiology, and End Results Medicare Database and medical chart-based comorbidity data collection by cancer registrars.

514 P16INK4a is a marker of good prognosis in primary invasive penile squamous cell carcinoma: A multi-institutional study

Purpose: We assessed the prognostic role of p16INK4a expression in penile cancer with respect to cancer specific survival.Materials and Methods: Based on a multi-institutional collaboration wax embedded tissues from 92 surgically treated patients, including 27 with total and 65 with partial penectomy, were retrospectively evaluated. After a central histopathological review by 1 pathologist a tissue microarray was constructed for p16INK4a immunostaining. Two independent pathologists evaluated p16INK4a expression, which was correlated with cancer specific survival. The κ statistic was used to assess interobserver variability. Univariate and multivariate Cox proportional hazards analysis was applied to assess the independent effects of prognostic factors on cancer specific survival during a median postoperative followup of 32 months (IQR 6–66).Results: The κ statistic revealed excellent interobserver agreement (κ 0.934, p <0.001). Two and 5-year cancer specific survival rates for the entire study cohort were...

P16INK4a is a Marker of Good Prognosis for Primary Invasive Penile Squamous Cell Carcinoma: A Multi-Institutional Study

We assessed the prognostic role of p16(INK4a) expression in penile cancer with respect to cancer specific survival. Based on a multi-institutional collaboration wax embedded tissues from 92 surgically treated patients, including 27 with total and 65 with partial penectomy, were retrospectively evaluated. After a central histopathological review by 1 pathologist a tissue microarray was constructed for p16(INK4a) immunostaining. Two independent pathologists evaluated p16(INK4a) expression, which was correlated with cancer specific survival. The κ statistic was used to assess interobserver variability. Univariate and multivariate Cox proportional hazards analysis was applied to assess the independent effects of prognostic factors on cancer specific survival during a median postoperative followup of 32 months (IQR 6-66). The κ statistic revealed excellent interobserver agreement (κ 0.934, p <0.001). Two and 5-year cancer specific survival rates for the entire study cohort were 86% and 74%, respectively. The 2 and 5-year rates for patients without and with p16(INK4a) expression differed significantly (73% and 57% vs 95% and 85%, respectively, p = 0.011). Univariate analysis revealed p16(INK4a) expression as a significant prognostic factor with respect to cancer specific survival (p = 0.018). Multivariate analysis identified koilocytosis (HR 0.24, 95% CI 0.07-0.83, p = 0.024), p16(INK4a) expression (HR 0.44, 95% CI 0.23-0.84, p = 0.013), and histological stage (HR 3.54, 95% CI 1.88-6.67, p <0.001) and grade (HR 2.47, 95% CI 1.00-6.09, p = 0.049) as independent prognostic factors for cancer specific survival. Results show that p16(INK4a) seems to be a prognostic parameter for primary invasive penile cancer with excellent interobserver reproducibility. At pathology laboratories without antibodies against p16(INK4a) conventional histological determination of koilocytosis by the pathologist also appears to provide important prognostic information for cancer specific survival.

Primary invasive squamous cell carcinoma of male bulbar urethra completely responded to concurrent chemoradiation therapy

Primary invasive squamous cell carcinoma of male bulbar urethra completely responded to concurrent chemoradiation therapy

The Prognostic Role of Human Papillomavirus in Patients With Vaginal Cancer

The objective of the study was to evaluate the association between human papillomavirus (HPV) infection and clinical-pathological parameters in primary squamous cell carcinoma of the vagina and assess the value of HPV infection as a prognostic parameter. In our retrospective study, we identified 37 consecutive patients with primary invasive squamous cell carcinoma of the vagina; 35 patients were eligible for further investigations. Human papillomavirus detection was assessed by in situ hybridization assays from paraffin-embedded tissue blocks. Human papillomavirus detection was correlated with clinical-pathological parameters by χ² and Fisher exact tests. Univariate log-rank tests and multivariate Cox regression models were used to evaluate the association between HPV infection and patient survival. Human papillomavirus DNA was detected in 18 (51.4%) of 35 cases. Human papillomavirus status did no influence clinical-pathological parameters, such as clinical stage (P=0.9), grade (P=0.9), and tumor size (P=0.18). Prognosis did not significantly differ between HPV-positive and HPV-negative tumors in the entire cohort; however, patients with unfavorable tumor stage (International Federation of Gynecology and Obstetrics stage≥III) and HPV positivity had improved disease-free (P=0.004) and overall survival (P=0.023). Human papillomavirus infection was frequently detected in squamous cell carcinoma of the vagina, and its presence may serve as a prognostic indicator in advanced stages.

A Clinicopathological Study of Primary Cutaneous Invasive Squamous Cell Carcinoma: Relationship between a New Clinicopathological Classification and Prognosis

A Clinicopathological Study of Primary Cutaneous Invasive Squamous Cell Carcinoma: Relationship between a New Clinicopathological Classification and Prognosis

Expression of epidermal growth factor receptor and vascular endothelial growth factor in vaginal squamous cell cancer

Primary invasive squamous cell carcinoma of the vagina is a rare neoplasm. Investigations concerning the potential of new therapeutic targets are limited. A total of 34 patients with primary invasive squamous cell carcinoma of the vagina was identified, who were treated at our institution between 1994 and 2008. Epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) expression was assessed using immunohistochemistry from paraffin-embedded tissue blocks. EGFR was expressed in 33 of 34 (97.1%) and VEGF was expressed in 12 of 34 cases (35.3%). There was no statistically significant relationship between clinicopathologic parameters (clinical stage, grading, tumor size), patient survival, and EGFR and VEGF expression. VEGF was moderate and EGFR was frequently expressed in invasive squamous cell carcinoma of the vagina. In our sample size, immunohistochemical staining was not statistically significantly associated with prognosis.

Alterations in the tumor suppressor gene p16 INK4A are associated with aggressive behavior of penile carcinomas

Alterations in the p16/cyclinD1/Rb and ARF/Mdm2/p53 pathways are frequent events in the pathogenesis of squamous cell carcinomas. Different mechanisms of p16 regulation have been described for penile carcinomas so far. Therefore, expression of p16 and p53 was immunohistochemically detected with monoclonal antibodies in 52 primary invasive penile squamous cell carcinomas. The carcinomas were analyzed for allelic loss (LOH) in p16(INK4A) and p53, as well as for mutations in the p16(INK4A) and the p53 gene. In addition, we examined the promoter status of p16(INK4A) by methylation-specific PCR. The presence of human papilloma virus (HPV) 6/11, HPV 16 and HPV 18 DNA was analyzed by PCR. Data were compared to clinical data. Concerning p16, 26 (50%) tumors showed positive immunohistochemistry, 32 (62%) tumors showed allelic loss and 22 tumors (42%) showed promoter hypermethylation. All tumors with negative p16 immunohistochemistry showed LOH near the p16(INK4A) locus and/or hypermethylation of the p16(INK4A) promoter. HPV 16 DNA was detected in 17 tumors, ten of them with positive p16 immunostaining. The remaining seven tumors with negative p16 staining showed allelic loss and/or promoter hypermethylation. Evidence of lymph node metastasis was significantly associated with negative p16 immunohistochemistry as well as with combined LOH and promoter hypermethylation (p = 0.003 and p = 0.018, respectively). Allelic loss around p53 was found in 22 tumors (42%), and seven mutations of the p53 gene could be demonstrated in our tumors. No correlations could be found between any p53 alteration and clinical parameters.

Collision Tumor of Primary Laryngeal Mucosal Melanoma and Invasive Squamous Cell Carcinoma with IL-17A and CD70 Gene Over-Expression

The most common primary malignancy of the larynx is the squamous cell carcinoma (SCC). The primary malignant melanoma is quite rare in this location. Less than 60 cases of laryngeal melanomas have been reported to date. To our knowledge, collision primary malignant melanoma and invasive squamous cell carcinoma in the vocal cords has not been reported. We report a 53-year-old male patient who was diagnosed with a collision tumor of laryngeal melanoma and invasive SCC. Multiple Th17 pathway related genes including CTLA-4, IL-17A-F, PLZF, FoxP3, RorγT, CD27, and CD70 were analyzed by reverse transcriptase-polymerase chain reaction (Rt-PCR) in this case. Both IL-17A and CD70 genes were detected in this case of collision tumor. The results may define useful biomarkers for early diagnosis of mucosal melanoma and open an immunotherapeutic field for clinical management with the potential benefit from the immunomodulators that enhance both genes.

HPV DNA detection and genotyping in 21 cases of primary invasive squamous cell carcinoma of the vagina

Primary invasive squamous cell carcinoma of the vagina is rare, and the role of human papilloma virus in its pathogenesis remains unclear. The aims of our study were to determine the distribution of human papilloma virus genotypes in 21 cases of primary invasive squamous cell carcinoma of the vagina and to correlate human papilloma virus genotype with histological subtypes. Patients' clinical records were reviewed for demographic data and the stage of the disease. Tumors (n=21) were classified according to the World Health Organization criteria. Human papilloma virus genotyping (INNO-LiPA HPV Genotyping) was performed in the whole series, and statistical analysis was performed with Fisher’s Exact Test and with Student’s t-test. The patients' age ranged from 36 to 88 (mean 65) years. Six cases were keratinizing squamous cell carcinoma, and 15 cases were non-keratinizing squamous cell carcinoma (seven non-keratinizing not otherwise specified, three basaloid, and five warty types). The median age of patients with keratinizing squamous cell carcinoma was 73.8 years and that of non-keratinizing squamous cell carcinoma patients was 61.5 years (P=0.08). Human papilloma virus DNA was detected in 17 cases (81%): 13 non-keratinizing squamous cell carcinoma (87%) and four keratinizing squamous cell carcinoma (67%) (P=0.31). The human papilloma virus genotypes identified were: 6, 11, 16, 18, 31, 33, 35, 40, and 58, with human papilloma virus 16 DNA the most prevalent (33%). Invasive squamous cell carcinoma of the vagina is frequently associated with human papilloma virus infection, and human papilloma virus 16 is the most common genotype. Although without statistical significance, keratinizing squamous cell carcinoma is more frequent in older patients, whereas non-keratinizing squamous cell carcinoma more frequently affects younger women. All studied histological subtypes are strongly associated with human papilloma virus infection.

Epidermotropic Metastases from Squamous Cell Carcinoma of the Lower Female Genital Tract Mimicking Primary Bowen's Carcinoma

Epidermotropic metastases from internal malignancies are exceedingly rare. We report a striking example of epidermotropic metastatic carcinoma of the lower female genital tract to the skin of the abdomen and groin. Atypical cells were scattered throughout the epidermis, mimicking Bowen's disease. Focally, islands of atypical squamous cells were also found in the adjacent dermis. Histopathologically, the lesion resembled a primary invasive squamous cell carcinoma. However, the clinical history of a metastatic carcinoma of the genitalia and the clinical presentation with multiple lesions militated against a primary squamous cell carcinoma and favored interpretation of the lesions as epidermotropic metastases.

Primary invasive ocular squamous cell carcinoma in a horse

A 12-year-old Haflinger gelding was presented to the veterinary medical teaching hospital of the University of Zurich with a light-pink raised mass on the temporal limbus and conjunctiva of the left eye. Squamous cell carcinoma was confirmed histologically after keratectomy and cryotherapy. Seven months later, a smooth pink, progressively enlarging mass was observed within the cornea of the left eye. Ultrasonographically, the mass was not only infiltrating the corneal stroma but seemed to protrude into the anterior chamber. The globe was surgically removed and submitted for pathology. A histologic diagnosis of corneal ocular squamous cell carcinoma with deep stromal invasion, infiltration of the uveoscleral meshwork and iridocorneal angle and resulting intraocular extension was made. This is the first detailed description of a limbal squamous cell carcinoma with invasion into the cornea and uvea in the horse.