The importance of combined HPV and CINtec® PLUS genotyping testing for p16 in women with cervical squamous cell carcinoma.

INTRODUCTION: Immunohistochemistry (IHC) for p16INK4A (p16) is a reliable surrogate test for the presence of a high-risk, potentially transformative human papillomavirus (HPV) infection in precursor and malignant lesions of the cervix. The purpose of this study was to evaluate changes in cervical cells caused by persistent HPV infection, by IHC (p16 protein) by comparison with HPV genotyping. PATIENTS, MATERIALS AND METHODS: The study included female patients aged between 26 and 57 years who presented to a public hospital, with complaints related to the genital area, namely vaginal bleeding and dyspareunia. After selecting the patients, samples were subjected to cytological testing and IHC for p16 and for the determination of HPV types. RESULTS: The relationship between HPV status and p16 status was statistically significant (p=0.0001), of the 41 patients, 53.7% were HPV positive, respectively 56.1% were p16 positive, the agreement relationship between the two indicators was very high (weighted kappa: 0.951). The clinical performance of CINtec® PLUS triage for p16 shows a high positive predictive value (PPV) and a high negative predictive value (NPV) of 95.7% and 100%, respectively, as regards HPV. CONCLUSIONS: The p16 marker (CINtec® PLUS) can be used as a prognostic biomarker and provides clinical usefulness through increased sensitivity (Se) and specificity (Sp) in the triage of women at risk of developing precancerous lesions, compared to cytology that is based on morphology, but has a rather low Se and high Sp, while HPV testing is very sensitive but slightly more specific.

Human Placenta and Evolving Insights into Pathological Changes of Preeclampsia: A Comprehensive Review of the Last Decade.

The placenta, the foremost and multifaceted organ in fetal and maternal biology, is pivotal in facilitating optimal intrauterine fetal development. Remarkably, despite its paramount significance, the placenta remains enigmatic, meriting greater comprehension given its central influence on the health trajectories of both the fetus and the mother. Preeclampsia (PE) and intrauterine fetal growth restriction (IUGR), prevailing disorders of pregnancy, stem from compromised placental development. PE, characterized by heightened mortality and morbidity risks, afflicts 5-7% of global pregnancies, its etiology shrouded in ambiguity. Pertinent pathogenic hallmarks of PE encompass inadequate restructuring of uteroplacental spiral arteries, placental ischemia, and elevated levels of vascular endothelial growth factor receptor-1 (VEGFR-1), also recognized as soluble FMS-like tyrosine kinase-1 (sFlt-1). During gestation, the placental derivation of sFlt-1 accentuates its role as an inhibitory receptor binding to VEGF-A and placental growth factor (PlGF), curtailing target cell accessibility. This review expounds upon the placenta's defining cellular component of the trophoblast, elucidates the intricacies of PE pathogenesis, underscores the pivotal contribution of sFlt-1 to maternal pathology and fetal safeguarding, and surveys recent therapeutic strides witnessed in the past decade.

Conventional Tools for Predicting Satisfactory Response to Neoadjuvant Chemotherapy in HR+/HER2- Breast Cancer Patients.

Aim: The aim of the study was to assess the role of Magee Equation 3 (MagEq3), IHC4 score, and HER2-low status in predicting "satisfactory response (SR)" to neoadjuvant chemotherapy (NAC) in HR+/HER2- breast cancer (BC) patients. Methods: In a retrospective study, female patients of any age with T1-4, N0-2, M0 HR+/HER2- BC who received NAC and underwent adequate locoregional surgical treatment were included. Patients were grouped according to 2 outcomes: (a) overall response to NAC in breast and axilla by using residual cancer burden (RCB) criteria and (b) axillary downstaging after NAC by using N staging. 2 cohorts for overall response were overall SR (RCB 0-1) and no SR (RCB 2-3). On the other hand, for axillary downstaging, 2 cohorts constituted from axillary SR (ypN0 and ypN0i+) and no SR (ypNmic-N3). MagEq3 and IHC4 scores were calculated from their pathological tumor slides in each patient. HER2 status was categorized as either "no" or "low." In addition, patient age, family history, tumor histology, stage at admission, and Ki-67 status were compared between cohorts according to predefined outcomes. Results: In a total of 230 BC patients, 228 patients were included to compare according to their RCB levels. The mean age of patients with overall SR was significantly lower than those without. Patients with high Ki-67 expression, high (>30) MagEq3 score, high ICH4 quartile, and HER2-low status had significantly more overall SR. On the other hand, only patients with high Ki-67 expression had significantly more axillary SR. MagEq3 score levels, ICH4 quartiles, and HER2 status were similar between patients with axillary SR and not. Conclusion: MagEq3 and IHC4 tools seemed to be useful to predict those HR+/HER2- BC patients who are most likely to get benefit from NAC. But, only high Ki-67 expression level significantly predicted satisfactory axillary downstaging in HR+/HER2- BC patients.

New Insights into Genetics of Endometriosis-A Comprehensive Literature Review.

This comprehensive review explores the genetic contributions to endometriosis and their potential impact on improving diagnostic techniques. The review begins by defining endometriosis and discussing its prevalence, emphasizing the need for a deeper understanding of the genetic basis of the condition. It highlights recent genome-wide association studies (GWAS) that have identified specific genetic variants associated with endometriosis, shedding light on the molecular pathways and mechanisms involved. The review addresses genetic heterogeneity across different populations and ethnicities, emphasizing the importance of considering population-specific markers in diagnostic approaches. It explores the diagnostic implications of genetic insights, including the potential use of genetic markers for precise and early detection, as well as risk prediction. The review also delves into the integration of genetic information with clinical parameters and imaging findings, and the exploration of multi-omics approaches for a comprehensive understanding of endometriosis. It discusses recent studies on genetic and epigenetic biomarkers, their potential as diagnostic tools, and the need for validation in independent cohorts. The review highlights the impact of new genomic technologies, such as next-generation sequencing, in improving diagnostic accuracy and personalized management. It identifies the challenges and future directions in translating genetic findings into diagnostic tools and emphasizes the transformative potential of genetic insights in endometriosis diagnosis. This review provides a roadmap for future research and underscores the significance of genetic insights in improving diagnostic precision and personalized care for individuals with endometriosis.

Immature Teratoma: Diagnosis and Management-A Review of the Literature.

An immature teratoma is a germinal malignant tumor composed of three germ cell layers, occurring more frequently in young women. It is the second most frequent among the malignant germinal tumors after dysgerminoma, and it is the only neoplasm with germ cells that are histologically graded. Even if we do not have a consensus regarding its therapeutical management, it has a good prognosis, with an excellent overall survival rate and good fertility preservation. More studies are needed regarding the necessity of adjuvant chemotherapy in pediatric oncology, and because of chemotherapy's long-term adverse effects, surveillance or a targeted treatment is preferred, but the main therapy is fertility-sparing surgery. Special attention should be given to the genetic mapping of the histological pieces for patient risk stratification due to its value in prognosis and future treatment.

The Approach of Artificial Intelligence in Neuroendocrine Carcinomas of the Breast: A Next Step towards Precision Pathology?-A Case Report and Review of the Literature.

Primary neuroendocrine tumors (NETs) of the breast are considered a rare and undervalued subtype of breast carcinoma that occur mainly in postmenopausal women and are graded as G1 or G2 NETs or an invasive neuroendocrine carcinoma (NEC) (small cell or large cell). To establish a final diagnosis of breast carcinoma with neuroendocrine differentiation, it is essential to perform an immunohistochemical profile of the tumor, using antibodies against synaptophysin or chromogranin, as well as the MIB-1 proliferation index, one of the most controversial markers in breast pathology regarding its methodology in current clinical practice. A standardization error between institutions and pathologists regarding the evaluation of the MIB-1 proliferation index is present. Another challenge refers to the counting process of MIB-1's expressiveness, which is known as a time-consuming process. The involvement of AI (artificial intelligence) automated systems could be a solution for diagnosing early stages, as well. We present the case of a post-menopausal 79-year-old woman diagnosed with primary neuroendocrine carcinoma of the breast (NECB). The purpose of this paper is to expose the interpretation of MIB-1 expression in our patient' s case of breast neuroendocrine carcinoma, assisted by artificial intelligence (AI) software (HALO-IndicaLabs), and to analyze the associations between MIB-1 and common histopathological parameters.

The Hybrid Capture 2 Results in Correlation with the Pap Test, Sexual Behavior, and Characteristics of Romanian Women.

BACKGROUND: Human papillomavirus (HPV) infection is the major cause of cervical cancer (CC); hence, it is critical to understand the processes by which HPV infection causes squamous intraepithelial lesions, as well as the proper diagnostic tools. The objective of this study was to establish the correlations between Pap test results and Hybrid Capture 2 (HC2) tests findings. MATERIALS AND METHODS: This study included 169 women between the ages of 30 and 64, who presented for consultation in gynecological clinics in both the public and the private sectors. These women reported symptoms, such as abnormal vaginal discharge and genital irritation, as well as early onset of sexual activity, multiple sexual partners, history of other sexually transmitted infections or high-risk sexual partners, immunosuppression, or tobacco smoking. Pap tests and HPV testing, using the HC2 method, were performed for the women enrolled in the study, including data gathered after patients completed questionnaires concerning their sexual behavior. RESULTS: The HC2 method revealed that 66 patients (39.1%) tested positive for high-risk HPV types. Of the patients with positive results, 14 (21.2%) presented Atypical Squamous Cells of Undetermined Significance (ASC-US) compared to 10 (9.7%) patients in the negative group (p = 0.042). Atypical Squamous Cells for which a high-grade lesion cannot be excluded (ASC-H) were identified primarily in women with positive HC2 (6.1%). HR-HPV positivity was substantially more associated with low-grade ASC-US or low-grade squamous intraepithelial lesion (LSIL) and high-grade ASC-H cytology (OR = 2.53; 95% CI: 1.10-5.80, respectively, OR = 14.9; 95%CI: 1.006-34.59). Unmarried women (31.8%; p = 0.004) and women with multiple partners (over four partners, 10.6%; p = 0.03) were more likely to have an HPV infection when compared to married women and those with fewer sexual partners. CONCLUSIONS: Understanding the epidemiology of HPV genital infections is essential for developing preventive measures against this infection and CC. Identifying the most prevalent HPV types, and determining the incidence of HPV oncogenic infections, in conjunction with Pap test results and sexual behavior information, can constitute part of an algorithm for the efficient management of cervical intraepithelial lesions.

Diagnosis and Management of Dysgerminomas with a Brief Summary of Primitive Germ Cell Tumors.

Dysgerminoma represents a rare malignant tumor composed of germ cells, originally from the embryonic gonads. Regarding its incidence, we do not have precise data due to its rarity. Dysgerminoma occurs at a fertile age. The preferred treatment is the surgical removal of the tumor succeeded by the preservation of fertility. Even if a multidisciplinary team, founded in 2009 by a gynecologist, an oncologist, a pediatric oncologist and a pediatric surgeon, under the guidance of the Malignant Germ Cell International Consortium (MaGIC), studies this type of tumor, issues still remain related to the lack of a randomized study and to both the management and understanding of the concept of OMGCTs (ovarian malignant germ cell tumors). The aim of this review is to present from the literature the various approaches for this type of tumor, and, regarding innovative therapies or possible prevention, which can be applied in clinical practice. Multidisciplinarity and treatment in reference centers have proven their usefulness as well.

The Role of p16/Ki-67 Immunostaining, hTERC Amplification and Fibronectin in Predicting Cervical Cancer Progression: A Systematic Review.

Human papillomaviruses (HPVs) are common sexually transmitted infectious agents responsible for several anogenital and head and neck cancers. Cervical cancer (CC) is the fourth leading cause of death in women with cancer. The progression of a persistent HPV infection to cancer takes 15-20 years and can be preventable through screening. Cervical cytology (Pap smear) is the standard screening test for CC and precancerous lesions. For ASC-US and ASC-H lesions, a combination of Pap smear and HR-HPV analysis is recommended as a triage step before colposcopy. However, these tests cannot predict progression to CC. For this purpose, we summarized current scientific data on the role of p16/Ki-67 immunohistostaining, telomerase and fibronectin in predicting progression to CC. p16 and p16/Ki-67 dual staining (DS) were more specific than HR-HPV DNA testing for the detection of CIN2+/CIN3+ in women with ASC-US and LSIL. Similarly, hTERC FISH analysis significantly improved the specificity and positive predictive value of HPV DNA testing in differentiating CIN2+ from CIN2 cytological samples. In conclusion, p16 IHC, p16/Ki-67 DS and hTERC FISH amplification are all valid adjunctive biomarkers which significantly increase the sensitivity and specificity of cervical dysplasia diagnosis, especially when combined with HPV DNA testing. However, considering the global socioeconomic background, we can postulate that p16 and p16/ Ki-67 IHC can be used as a next step after positive cytology for ASC-US or LSIL specimens in low-income countries, instead of HPV DNA testing. Alternatively, if HPV DNA testing is covered by insurance, p16 or p16/Ki-67 DS and HPV DNA co-testing can be performed. In middle- and high-income countries, hTERC amplification can be performed as an adjunctive test to HPV DNA testing in women with ASC-US and LSIL.

A Race against the Clock: A Case Report and Literature Review Concerning the Importance of ADAMTS13 Testing in Diagnosis and Management of Thrombotic Thrombocytopenic Purpura during Pregnancy.

Thrombocytopenic purpura (TTP) is a rare, potentially fatal pathology characterized by microangiopathic thrombotic syndrome and caused by an acute protease deficiency of von Willebrand factor, ADAMTS13. Moreover, ADAMTS13 deficiency promotes microthrombosis led by the persistence of ultra-large VWF multimers in the blood circulation. According to the few studies involving pregnant participants, the heterogeneity of manifestations has made this pathology difficult to diagnose, with an unexpected occurrence and increased risk of maternal and fetal morbidity and mortality. We reported on the case of a 28-year-old pregnant woman with an obstetric score of G2P0 who presented to the obstetrics and gynecology department of our clinic with the complaint of minimal vaginal bleeding. The evolution of our case was severe and life-threatening, a "race against the clock", with our goal being to emphasize the importance and difficulty of diagnosing TTP in the absence of specific symptomatology. We faced a lack of technological support for a correct and complete diagnosis, and the first manifestation of this disease was the intrauterine death of the fetus. After completing all the necessary procedures, the placental tissue was sent for further histopathological evaluation. We highlighted the importance of monitoring ADAMTS13 for relapses monthly, with prophylaxis being essential for maternal and fetal mortality and morbidity.

Atypical Polypoid Adenomyoma of the Vagina: Follow Up and Subsequent Evolution: A Case Report and Update.

Atypical polypoid adenomyoma (APA) is a rare tumor developed from a mix of cells of epithelial and mesenchymal origin. We present the case of an 84-year-old patient with atypical polypoid adenomyoma on the vaginal vault, after total hysterectomy with total adnexectomy for endometrial hyperplasia with atypia four years ago. Not following regular indicated gynecological appointments, the symptoms presented were vaginal bleeding and anemia. The importance of the case consists both in the unique way in which the adenomyoma appears on the vaginal vault and in the subsequent evolution of this pathology. After complete resection, it recurs in five months with a malignant transformation into carcinosarcoma. This fact shows that adenomas can turn not only into carcinomas but also the mesenchymal component can progress to sarcoma, a fact of exceptional rarity. Follow-up and accurate diagnosis are essential for proper management, which is a challenge anyway due to the lack of case studies.

CK 8∕18: the key to differentiating intracutaneous lesions with pagetoid features.

INTRODUCTION: Neoplasms with pagetoid features are a category of rare lesions defined by the presence of atypical cells at different levels of the epidermis. The most important diseases within this category are mammary Paget disease (MPD), extramammary Paget disease (EMPD), Bowen's disease, in situ melanoma, and pagetoid reticulosis. AIM: The aim of this analysis was to describe the importance of the cytokeratin 8∕18 (CK 8∕18) immunostaining in diagnosing MPD and EMPD and differentiating them from other lesions. MATERIALS AND METHODS: A retrospective study was employed, based on the histopathological and immunohistochemical (IHC) characteristics of 30 cases that presented pagetoid features. The cases were processed and analyzed at the Department of Pathology, Mures Clinical County Hospital, Târgu Mures, Romania, from 2017 to 2020. RESULTS: Five MPD cases, one EMPD case, one pagetoid reticulosis case, 10 Bowen's disease cases, and 13 in situ melanoma cases were collected. Under Hematoxylin-Eosin staining, cells presented pale cytoplasm in MPD, EMPD, and in 25% of the melanoma cases. Hyperchromasia with nuclear enlargement was seen in all cases. Immunostaining with CK 8∕18 was positive in all MPD and EMPD cases. Tests for CK7, p63, and CK AE1∕AE3 were positive in MPD, EMPD, and Bowen's cases. Tests for S100, SRY-box transcription factor 10 (SOX10), human melanoma black 45 (HMB45), and Melan A were positive in melanoma cases, while cluster of differentiation (CD)3, CD4, and CD8 tests were positive in the pagetoid reticulosis case. CONCLUSIONS: CK 8∕18 is an IHC marker that can help establish the diagnosis of MPD and EMPD and differentiate them from other pagetoid neoplasms, ensuring the proper diagnosis and prognosis are provided.

Lung injury patterns in newborns, infants and young children - morphological and immunohistochemical approaches.

Lower respiratory infections are an important cause of morbidity and mortality in children, especially in newborns, infants and young children. We conducted a retrospective study and we analyzed the causes of death in newborns, infants and young children, in the necropsy protocols from two Departments of Pathology (Mures County Hospital and Emergency County Hospital of Târgu Mures, Romania), between 2016-2018. We performed descriptive statistics: number of necropsies per year, distribution by gender (male∕female), by place of origin (rural∕urban), by age and leading causes of death in our study. To establish the pattern of lung injuries, we performed a morphological, histopathological and immunohistochemical study [cluster of differentiation (CD) 3, CD14, CD20, CD31, CD34, CD68]. Our study is showing the most frequent and typical aspects of pulmonary pathologies in fetuses, newborns, infants and young children. In this way, we are highlighting the microscopic aspects of the immature lung, amniotic fluid and meconium aspiration, pulmonary distress syndrome in children, pneumonia, bronchopneumonia and vascular pulmonary disease developed in patients with congenital cardiac defects. Most deaths were recorded in the first 30 days or in the first year of life. Primary respiratory diseases were the leading causes of death in these patients. Secondary respiratory diseases were associated with the major causes of death in these patients as an aggravating or precipitating factor.

Immunohistochemical expression of Ki-67 and p53 along with their digitalized evaluation in the discriminatory analysis of reactive atypia and dysplastic lesions in gastrointestinal biopsies of the stomach.

The differential diagnosis between reactive atypia and non-invasive neoplasia (or dysplasia) can be challenging in the case of small conventional forceps biopsy specimens of the stomach. Despite the existence of several classifications for neoplastic epithelial lesions of the stomach, there are few auxiliary tools for aiding in this decision besides standard stains. We studied the utility of Ki-67 and p53 immunohistochemistry in this setting and their clinico-pathological correlations, based on a set of 99 cases with cytological or architectural atypia reviewed by three pathologists. We also tested a digitalized method based on the ImageJ software for the evaluation of Ki-67 expression to determine whether this could be of an additional help. CONCLUSIONS: Ki-67 and p53 expression correlates well with microscopic and morphological modifications in biopsies and can be a useful tool in confirming or dismissing an impression of dysplasia in routine pathological work-up. Digital processing is cumbersome and of limited value and it could only be of additional help if more automated methods are developed.

Different synovial vasculogenic profiles of primary, rapidly destructive and osteonecrosis-induced hip osteoarthritis. An immunohistochemistry study.

PURPOSE: To present a hypothesis regarding the pathways of angiogenesis in primary versus secondary hip osteoarthritis (OA). METHODS: In synovial tissue samples provided by 57 consecutive patients who underwent hip arthroplasty, immunohistochemical examinations were performed using the following angiogenesis-related antibodies: VEGF-A, COX-2, maspin and the endothelial cells markers CD31 and CD105. The cases were divided into three categories: classic primary hip OA (group A; n = 16), rapidly destructive hip OA (group B; n = 24) and hip OA secondary to avascular osteonecrosis of the femoral head (group C; n = 17). The endothelial area (EA) was digitally quantified for both CD31 and CD105. RESULTS: The large mature vessels with CD105-positive activated endothelium predominated in group C, which also showed the highest CD105 median EA value (7.31 ± 4.01, compared to 4.76 ± 3.73 for group A and 6.69 ± 3.53 for group B). In groups A and B, synovial cell hyperplasia and the predominance of small immature vessels were characteristic. CD105, VEGF-A and COX-2 were focally seen in the synovial membrane, without maspin positivity. CONCLUSIONS: The severity of hip OA can be related to angiogenesis pathways that are not maspin-mediated. In primary hip OA, angiogenesis may be induced by a combined mechanism: hypoxia-related VEGF-dependent vasculogenesis and endothelial differentiation of the activated pluripotent cells, which are released from the hyperplastic synovial cells layer. An endothelial mesenchymal transition is assumed to be involved in the fibrotic process.

Histopathological evaluation and expression of the pluripotent mesenchymal stem cell-like markers CD105 and CD44 in the synovial membrane of patients with primary versus secondary hip osteoarthritis.

To present the morphological changes of classic primary versus rapidly progressive and secondary hip osteoarthritis (HO) and to examine the expression of two pluripotent mesenchymal stem cell-like markers in the synovial membrane. A prospective observational study was conducted in 57 consecutive cases of radiologically confirmed HO in which total hip arthroplasty was performed. Based on the radiological and clinicopathological features, the cases were divided into three categories: classic primary HO (group A; n=16), rapidly destructive HO (group B; n=24), and HO secondary to avascular osteonecrosis of the femoral head (group C; n=17). Immunostains were performed using the markers CD44 and CD105. The cases from group A were mainly characterized by a marked perivascular inflammatory infiltrate and simple synovial hyperplasia. In group B, the papillary type of synovial hyperplasia was found and presence of chondromatosis, ossification, and ectopic follicles with germinal centers in the subsynovial layer was characteristic, whereas marked calcification and/or ossification were seen in group C. Focal expression of the CD105 and CD44 was noted in the hyperplastic synovial cells and subsynovial layer in cases from group A, whereas synovial cells from group B were diffusely positive for both CD44 and CD105. In secondary HO, CD44 marked the inflammatory cells. Mobilization of the CD44/CD105 positive synovial cells seems to play a role in the genesis of HO. The number of the pluripotent mesenchymal stem cell-like cells derived from the hyperplastic synovial cells might be related to the severity of possible immune-mediated rapidly destructive HO.

Unexpected maspin immunoreactivity in Merkel cell carcinoma.

Merkel cell carcinoma (MCC) is a rare but aggressive cutaneous neuroendocrine tumor, which multifactorial etiopathogenesis seems to be related to ultraviolet radiation, Merkel cell polyomavirus (MCV), and immunosuppression. In this paper, we present three cases of diagnosed MCC in apparently healthy Caucasians, two of them located in a sun-exposed area. They represented 0.25 % of all cutaneous malignant tumors diagnosed in our department. In the first case, MCC was diagnosed in the frontal region of a 67-year-old male, the second case was located in the right thigh of a 55-year-old female, whereas the third case involved the upper trunk of a 62-year-old female. All of these cases were diagnosed in the pT1 stage, having a diameter smaller than 2 cm, but the invasion depth involved the hypodermis. Microscopically, they consisted of small cells with round-oval nuclei having finely dispersed chromatin and well-defined nucleoli. Immunohistochemically, the tumor cells displayed positivity for keratin 20 and neuroendocrine markers, being negative for keratin 7 and S100 protein. Maspin immunoreactivity was seen in cases 1 and 3. Not one of the cases expressed DOG-1 or even TTF-1. Furthermore, this is the first report in literature about maspin positivity in MCC that might be related to sun exposure.

Correlation of angiogenesis with other immunohistochemical markers in cutaneous basal and squamous cell carcinomas.

UNLABELLED: The aim of this study was to establish an immunoprofile of squamous cell carcinoma (SCC) and basal cell carcinoma (BCC), and to explore as first time in literature the possible correlation between maspin, DOG-1, p16 protein and angiogenesis in these tumors. For SCCs, the histological grade of differentiation was also taken into account. The angiogenesis was quantified in 38 randomly selected cases of SCCs and 17 BCCc, respectively, using the antibodies vascular endothelial growth factor (VEGF-A) and COX-2, while the microvessel density (MVD) was evaluated with the CD31. RESULTS: In SCCs, maspin cytoplasm to nuclear shift was an indicator of a deeper tissue invasion and dedifferentiation in the invasion front. The poorly differentiated cases, compared to G1÷G2-SCCs, expressed more frequent the markers p16 (30.77% vs. 8%) and VEGF-A (53.85% vs. 32%), regardless the MVD. However, the p16 positivity was more frequent in BCCs than SCCs (52.94% vs. 15.79%). All of the p16-positive carcinomas were located in the head and neck area. DOG-1 marked 21.05% of SCCs and 5.88% of BCCs, being directly correlated with COX-2 positivity. Eccrine glands and hair follicles also expressed DOG-1. CONCLUSIONS: In cutaneous SCCs located in the head and neck area, sun-dependent p16÷VEGF interaction seems to be responsible by tumor dedifferentiation, whereas maspin cytoplasm to nuclear shift might indicate a high degree of invasiveness. This is the first report about DOG-1 positivity in BCCs and eccrine glands, the significance of this pattern being unknown.