Acral Verrucous Carcinoma.

INTRODUCTION: The verrucous carcinoma is a type of squamous carcinoma that is highly differentiated, relatively uncommon, locally aggressive, with slow growth and minimal metastatic potential. CLINICAL CASE: A 48-year old man was admitted to the Dermatology department of the Craiova Hospital for a round-oval tumoral mass that was hyperkeratotic, with central ulceration, covered by a hematic crust, approximately 1.5cm in size, localized at the distal phalanx of the third finger left hand, with perilesional edema and erythema. The wart-like lesion appeared 8 months beforehand, which the patient has traumatized repeatedly in the last 2 months. The histopathological examination confirmed the diagnosis of verrucous carcinoma. The X-ray examination revealed external margin osteolysis of the distal epiphysis in the third finger, left hand. The patient was transfered to the Plastic surgery department where the distal phalanx of the third finger, left hand was amputated. DISCUSSIONS: Risk factors for the development of verrucous carcinoma are HPV infection, carcinogenic chemicals, smoking, chronic inflammation, repeated trauma, etc. Diagnosis is suspected by clinical appearance and confirmed histopathologically. The treatment of choice is surgical excision due to the high risk of recurrence and local invasiveness, and in the case of an advanced tumor with acral localization, amputation is preferred, as is our case. CONCLUSIONS: Verrucous carcinoma is a type of squamous carcinoma that is highly differentiated, with slow and continuous invasion of the underlying tissues. In order to establish the diagnosis of verrucous carcinoma, it is necessary to corroborate the clinical examination with histopathological and evolutionary examinations. The treatment of choice is surgical excision, but given the increased risk of recurrence, the patient should be evaluated periodically until complete healing. Our case is interesting by localization and rapid evolution with the invasion of the underlying tissues.

Clear Cell Acanthoma with Atypical Location -Case Report and Literature Review.

Clear cell acanthoma is an uncommon, benign lesion, usually present in middle-aged and elderly patients. It looks like an erythematous papule, solitary, with squama at the periphery, regularly located on the lower limbs. We present the case of an 80-year-old female, who was admitted in the Dermatology Clinic of Craiova for an infiltrative plaque, erythematous-squamous-crusty, well delimited, with sizes 1,2/1,5cm, polycyclic shape, located in the right groin. The onset of the condition was 7-8 years ago, with slow growth in size. The excision of the lesion was performed and the histopathological examination confirmed the diagnosis of clear cell acanthoma. Our case is atypical by location. Because clear cell acanthoma is difficult to be clinically diagnosed, with a wide range of lesions that make a differential diagnosis, we highlight the importance of histopathological examination for a positive diagnosis. The treatment depends on the type of lesion and on the patient's preference, usually consisting in surgical excision.

The Role of Podoplanin in the Lymphangiogenesis of Oral Squamous Carcinomas.

Oral squamous cells carcinoma (OSCC) mortality rate ranges between 29-40/100,000 inhabitants. Regional lymph node metastases occur in 30-40% cases and are associated with unfavorable prognosis and decreased survival. Recentely it was suggested that the tumor-associated lymphatic vessels formation plays an active role in metastasis proces of several human malignancies, including OSCC. In the present study we investigated comparatively podoplanin immunoexpression in OSCC in both the tumor cells and lymphatic vessels reported to clinicopathological prognostic parameters. Material and methods The study included a total of 25 cases of OSCC. We investigated clinico-pathological parameters as age, gender, tumor site, and degree of differentiation, size and depth of invasion (pT), lymph node status (pN). Histologic classification was done according to the WHO criteria. For immunohistochemical (IHC) analysis we used podoplanin (Dako, clone D2-40). As visualization system it was used LSAB2 (Dako, Redox, Romania, code K0675) and chromogen DAB (Dako, Redox, Romania, code K3468). Negative controls were obtained by omitting the primary antibodies. IHC quantification was done intensity score and by lymphatic microdensity (LVD), intratumoral and on the advancing edge. For the statistical analysis we used Student's t-tests, ANOVA, chi square and Pearson, using SPSS 10 software. Results Podoplanin immunoexpression in tumor parenchyma presented with an average of 43%, varying intensity. We found a higher intensity in weak and moderately differentiated SCC then in well differentiated ones and no difference intratumoral aand advancing edge. In relation to the degree of tumor differentiation the mean LVD D2-40 was higher in the advancing edge. SCC who presented lymph node metastasis mean values for LVD D2-4 was higher then at advancing edge and higher than those of non-metastatic carcinomas. Conclusions Podoplanin immunoexpresion suggests the involvement both in tumor growth and the acquisition of an lymphangiogenic phenotype invasive by autocrine mechanisms.

Correlation between High Endothelial Vessels and Histopathological Features of Different Pigmented Lesions.

PURPOSE: Tumor infiltrating lymphocytes are playing an important role in cutaneous melanoma being a strong prognostic parameter. Our goal was to study the presence of high endothelial vessels in correlation with the histopathological features in different pigmented skin lesions. MATERIAL AND METHODS: our study group included 60 patients (20 cases with dysplastic nevi, 20 thin melanoma and 20 thick melanoma). For each patient we noted epidemiological and clinico-pathological characteristics including: age, gender, anatomic sites, regression, Breslow thickness, mitoses, Clark level and lymphocytic infiltration. Using immunohistochemistry staining we identified the presence of high endothelial vessels in our groups. RESULTS: the most common localization of primary melanoma was trunk 57,5%, followed by extremities 35% and head 7,5%. We found positive MECA-79 vessels in 67% of primary melanoma samples and in 30% of dysplastic nevi. Lymphocytic infiltration was present in 80% samples of dysplastic nevi and 75% of primary melanomas. Using Kruskal Wallis non-parametric test we found a positive association between MECA-79+ vessels and different anatomic sites (p<0,01). We have also found a significant correlation between MECA-79+ vessels and the presence of regression in melanoma samples. In conclusion a better understanding of tumor microenvironment and mechanisms involved in anti-tumor response might play an important role in development of future melanoma therapeutic strategies.

Bullous pemphigoid associated with psoriasis, breast cancer and Parkinson's disease.

Bullous pemphigoid (BP) and psoriasis vulgaris represent two clinically well characterized, inflammatory, chronic skin diseases. A 62 years old female patient, from rural areas, was admitted for the presence of erythematous plaques covered by large tense blisters with clear fluid, located symmetrically on the anterior part of the upper limbs, the trunk, the neck and the lower limbs. Also the lesions were intense itching. Lesions occurred three days before presentation at the clinic. Medical history revealed psoriasis diagnosed 28 years ago, breast cancer treated with surgery, radio and chemotherapy three years ago and Parkinson's disease diagnosed 3 weeks prior to presentation to the dermatology clinic. Histopathology examination revealed: atrophic epidermis with subepidermal presence of a blister containing numerous eosinophils and neutrophils. In the papillary dermis neutrophils and eosinophils predominantly vascular. Bullous pemphigoid has multiple etiology. Bullous pemphigoid is an autoimmune subepidermal bullous dermatosis which may be associated with psoriasis. Medical literature and cases reported in dermatology journals claim that bullous pemphigoid is often associated with psoriasis, though the immunogenetical and immunopathologycal mecanismes are still not known. Our patient has three different diseases but their etiology and pathogenesis can interfere.

Disseminated granuloma annulare: study on eight cases.

Granuloma annulare (GA) is classified as localized, generalized/disseminated, subcutaneous, and perforating types. The studies show connection with diabetes mellitus, lipidic metabolic disorders, malignant diseases, thyroid disorders, infections (HBV, HCV, HIV). We performed a retrospective study between 2010-2011, regarding disseminated GA (GAD), and the relationship between GAD and other comorbidities. We clinically and histologically diagnosed eight cases of GAD. The patients were also investigated for the diagnosis of associated diseases. The treatment included topical corticosteroids, antihistamines, Calcipotriol/Betamethasone, Tacrolimus 0.03%, Pentoxifylline, Hydroxychloroquine. Therapeutic response was assessed one month and three months after hospitalization. Our patients were five women and three men, aged 46-68 years, mean age 57.25 years, with a disease history of one year and a half (between three months and four years). The lesions occurred in the upper extremities (eight cases), distal extremities (three cases), cervical area (two cases), and trunk (five cases). In seven cases, we found annular appearance and one patient had disseminated small papules eruption. Associated pathology was diabetes mellitus type II (five cases), overweight and obesity (five cases), dyslipidemia (three cases), hypothyroidism (one case), rheumatoid arthritis (one case), external ear canal basal carcinoma (one case). Although there is controversy regarding the relationship between GAD and associated diseases, it is accepted that it is significantly associated with diabetes mellitus, also found in our study in five out of eight cases. We noticed obvious improvements after local and general treatment. It is confirmed that GAD is prevalent in women, over 40-year-old. GAD is often associated with diabetes and dyslipidemia, therefore it is necessary to investigate patients in this direction. The histopathological exam is essential for an accurate confirmation of GA.

Lymphatic microvessels density, VEGF-C, and VEGFR-3 expression in 25 cases of breast invasive lobular carcinoma.

Invasive lobular carcinoma (ILC) is the second most common type of invasive breast cancer, having distinct morphologically but also prognostic and therapeutic features. This type of breast cancer shows a higher rate of multiple metastases with a more frequent axillary-lymph-node involvement. Related to these dissemination and metastatic features, we aimed to study the immunohistochemical expression of D2-40, VEGF-C and VEGFR-3 in 25 cases of ILCs stratified according to the histopathological and molecular classification. Regardless of histopathological or molecular subtype, the statistical tests proved that for ILC, the highest D2-40 lymphatic microvessels density (LMVD) was in the peritumoral areas. In classical subtype, the LMVD values were positively correlated with the degree of tumor differentiation and pTNM clinical stages and when these cases were classified based on the molecular criteria the highest recorded values were found in the luminal B subtype. In addition, regardless of the histopathological and molecular subtypes, the D2-40 LMVD varied in the same direction for both VEGF-C and VEGFR-3 categories, with the highest LMVD values recorded in those cases with the highest VEGF-C and VEGFR-3 reactivity, especially in the peritumoral areas. Considering only the molecular luminal A and B subtypes, we have noted that VEGF-C and VEGFR-3 expression was significantly higher in luminal A subtype compared to luminal B. This immunoprofile suggests the existence of a tumor type-specific lymphangiogenesis that may have certain prognostic and therapeutic implications.

Expression of CXCR4, MMP-13 and ß-catenin in different histological subtypes of facial basal cell carcinoma.

Basal cell carcinoma (BCC) is one of the most common skin neoplasms in humans, accounting for almost 80% of all non-melanoma skin cancers worldwide. The nodular and infiltrative-morpheaform are the most common BCC types in the head and neck region and together with the micronodular subtypes are the most aggressive tumors, because of their tendency to infiltrate the deep subcutis, muscles and even bones. To explain the local aggressive behavior and their metastatic potential, many studies have been performed to identify the molecular determinants implicated in BCC tumor progression. For this reason, we investigated the immunohistochemical expression of CXCR4, MMP-13 and ß-catenin expression in six metatypical, eight infiltrative-morpheaform, six micronodular and five superficial facial BCCs. For all three markers, the tumor reactivity varied with the histological type. The highest reactivity was observed in metatypical subtype, especially at the level of areas with squamous cells differentiation. The lowest reactivity was recorded in micronodular and superficial BCC subtypes. Regardless histological subtype, the tumor reactivity was higher at the advancing edge and additional a strong stromal reaction was noticed for all investigated markers peculiar in fibroblasts, inflammatory cells and endothelial cells. All these data proved the utility of CXCR4, MMP-13 and ß-catenin immunohistochemical investigation in BCCs both for identification of high-aggressive tumors and to develop novel more efficient therapeutic strategy for these patients by targeting these biomarkers.

The value of the histopathologic examination in the diagnosis and management of the actinic keratosis.

Actinic keratosis, considered lately as an intraepithelial squamous cell carcinoma in evolution, are powerful predictors of the risk for developing a cutaneous carcinoma and melanoma. The aims of the study were to establish the value of the histopathologic examination as a confirmation method for the actinic keratosis diagnosis, to assess the percentage of these lesions that suffer a malignant transformation, and also the frequency of the association between actinic keratosis and cutaneous carcinomas. This is a retrospective study, performed on 208 patients diagnosed with different types of cutaneous precancers, hospitalized in Dermatology Clinic of Craiova, Romania, between 2006 and 2010. Actinic keratosis represented 37.93% (79 cases) of all cutaneous precancers (the most frequent cutaneous precancer). Patient's age ranged from 17 to 85 years, 54.8% of the patients being from rural environment; 86.07% of the lesions were located on the solar exposed skin (head and face). 72.16% of the actinic keratosis was clinical subdiagnosed. The most frequent form was hypertrophic actinic keratosis (89.06%); in 18.98% of cases, malignant transformation in squamous cell carcinoma was noticed. Actinic keratosis represent 86% of the precancers that associate a carcinoma, basal cell carcinoma being diagnosed the most frequent. In conclusion, actinic keratosis are the most frequent cutaneous precancer, diagnosed in chronic sun-exposed patients, and manifest a tendency to progress into a squamous cell carcinoma without a proper treatment. Pathologic evaluation is mandatory to an accurate assessment of the actinic keratosis prevalence, and for the right management of these lesions.

Histopathological and clinical-progressive profile of skin carcinomas: study on 1688 cases.

Skin carcinomas represent 90-95% of skin cancers. With the objective of identifying the histopathological and clinical-progressive profile of skin carcinomas, we undertook a retrospective study over a period of seven years, which included a total of 1688 patients with carcinoma of the skin, hospitalized and treated in Craiova Dermatology Clinic between January 1999 and December 2006. Patient data such as identification data, environment, profession, phototype, location of cancer, history of the disease, clinical diagnosis, histopathological diagnosis and response to treatment were included in clinical charts. Basal cell carcinoma (BCC) was diagnosed in a total of 1162 patients, representing 68.84% of cases taken to the study. The most common clinical forms were: pearly BCC (37.95%), nodular BCC (29%), and superficial BCC (22.03%). Regarding the histological type, the most frequent forms were: BCC polymorphic (29.95%), BCC solid (24.96%), and keratinized BCC (19.97%). Epidermoid carcinoma (EC) was encountered in a total of 482 patients, representing 28.55% of all cases. The most frequent forms were: vegetated ulcerated EC (34.03%), nodular EC (31.33%) and keratosic EC (24.27%). Regarding the degree of differentiation, the situation was as follows: well-differentiated EC (64.94%), medium differentiated (29.88%), poorly differentiated (5.18%). Metatypical carcinoma (MC) was found in 44 patients (2.61%). This type of cancer did not presented clinical particular signs, the diagnosis was strictly pathological.

Basal cell carcinomas - clinical-evolutional and histopahotologic aspects.

Basal cell carcinoma (BCC) is the most frequent cutaneous tumour. Having as aim the identification of the clinical-evolutional and histopathologic aspects of the basal cell carcinomas, we have undertaken a retrospective study for a period of 5 years, from 1st January 2004 to 31st December 2008, on 706 patients interned in the Dermatology Clinic of Craiova, whom indicated 738 tumours. A clinical data was drawn for the patients, containing the identification data, environment, profession, cancer localisation and history of the disease, clinical and histopathologic diagnosis. Results. In our lot, the most numerous cases were of pearly BCC (33.6%), nodular BCC (22.2%), respectively scar plane BCC (13.1%).Regarding the histopathologic type, the repartition was as it follows: solid BCC (33.7%), polymorph (19.2%), adenoid (13.1%), keratinised (11.8%), superficial (7.0%), cystic (3.8%), pigmented (3.8%), scleroderma form (2.2%), in situ (1.4%).

Metastasized squamous cell carcinoma developed on lupus vulgaris.

Lupus vulgaris (LV) is the most frequent cutaneous tuberculosis, representing more than 55% of the tuberculoses with this location. Malignization can occur after a long latency (10-30 years), in 1-2% of the cases, and it is mainly in squamous cell carcinoma. The histological exam is highly important in the observation of neoplasic transformations. The authors present a 59-years-old female patient, from the rural environment, working as a farmer, with lupus vulgaris developing since her first childhood years. It started at the age of 2 years, at the right ear lobule, after the empiric perforation for earrings. The evolution was progressive, eccentric, interesting the pinna and the right cheek in the meanwhile. At the first examination, in 2002, a diffuse mass of red-yellowish infiltration was found at the level of the right ear and the right cheek. In the following two years, an ulcero-vegetating tumor developed at the level of the right ear lobule, accompanied by the presence of a right retromandibular adenopathy, of about 1 cm, which was proved by the histopathologic exam to be a squamous cell carcinoma developed from a lupus vulgaris. After scraping out the right retromandibular ganglion, detected by palpation, a histological exam showed ganglion metastasis.

The place of the histopathologic exam for establishing the profile of the squamous cell carcinoma of the lower lip with a high degree of malignity.

UNLABELLED: The squamous cell carcinoma of the lip has a metastasizing potential by lymphatic or/and sanguine ways. OBJECTIVE: Knowing the profile of the squamous cell carcinoma of the lip with a high degree of metastasizing. PATIENTS AND METHOD: We have analyzed on a group of 322 patients the influence of the degree of the histological differentiation of the tumor and the influence of the seriousness of the invasion over the metastasized potential. The bioptic fragments have been processed according to the usual histological technique paraffin embedding, and the sections have been colored with Hematoxylin-Eosin. Some of the cases have been immunomarked, to confirm the diagnosis, with antibody anti-cytokeratins, anti-vimentin, anti-protein S100 and anti-alpha actin. RESULTS: 12.24% of the patients with tumors with Broders II degree, 28.5% of those with Broders III degree and 52.94% of those patients with Broders IV degree presented metastasis, that show that the incidence of the regional ganglionary metastasis is higher in the case of the tumors with a low histological differentiation (test chi(2), p<0.001). 1.88% of the patients with an invasive squamous cell carcinoma under 6 mm and 38.60% of those with tumors of over 6 mm presented metastasis, that show that the risk of metastasizing is higher when the profoundness of the invasion is over 6 mm (test chi(2), p<0.001). In two cases we faced the changing of the malignity degree, meaning that it got worse passing from the Broders III degree (primary tumor) to Broders IV degree (relapse of the tumor). CONCLUSIONS: The histological differential degree of the tumor and the profoundness of the invasion are two important parameters when shaping the profile of the squamous cell carcinoma of the lip with a high degree of metastasis. The degree of malignity of the tumor may worsen during the evolution of the lip cancer, raising the risk of metastasizing as well.