Annular lichenoid dermatitis of youth-Recurrent case of rare skin disease treated with cyclosporine.

Annular lichenoid dermatitis of youth (ALDY), first described in 2003, represents an uncommon entity whose etiopathogenesis is still debated. Futhermore, the optimal treatment for ALDY is yet to be established. We report a 9-year-old girl who presented with annular and oval erythematous lesions mostly on her trunk, with several lesions on the neck, groin, flanks, and upper extremities. The lesions had histological and immunohistochemical features characteristic for ALDY. Treatment with H1-antihistamines, topical corticosteroid, and UVB therapy was unsuccessful, while systemic treatment with cyclosporine induced complete remission.

Expression of p300 and p300/CBP associated factor (PCAF) in actinic keratosis and squamous cell carcinoma of the skin.

p300 and p300/CBP-associated factor (PCAF) are histone modifiers and transcriptional co-factors involved in a number of cell processes. We investigated their expression patterns in 79 actinic keratoses (AK), 45 cases of Bowen's disease (BD), and 168 invasive squamous cell carcinomas of the skin (SCC). Using tissue microarray and immunohistochemistry, we evaluated p300 and PCAF expression in relation to the type of the lesion and SCC prognostic parameters (grade, diameter, thickness and level of invasion). High nuclear expression of p300 (>60% of positive cells) (p=0.001) and absent cytoplasmic expression (p=0.026) were more frequent in SCC compared to AK and BD, respectively. Cytoplasmic expression of p300 was associated with the SCC invasion of subcutaneous fat and deeper tissues (p=0.049). Diffuse distribution of cells with p300 nuclear expression was more commonly seen in BD and SCC compared to AK (p<0.001), in moderately- and poorly-differentiated SCC compared to well-differentiated SCC (p<0.001), in tumors thicker than 6mm (p<0.001), and in deeply invading tumors (p=0.001). More frequent loss of PCAF nuclear expression was observed in SCC than in AK and BD (p<0.001). Diffuse distribution of cells with PCAF cytoplasmic expression was more common in BD and SCC compared to AK (p<0.001), and in poorly-differentiated SCC compared to well- and moderately-differentiated SCC (p<0.001). Our results suggest that increase in nuclear expression of p300, as well as the presence of cytoplasmic but loss of nuclear expression of PCAF, could play an important role in the development and progression of cutaneous SCC.

Expression of G1/S-cyclins and cyclin-dependent kinase inhibitors in actinic keratosis and squamous cell carcinoma.

BACKGROUND: Actinic keratosis (AK) and Bowen's disease (squamous cell carcinoma in situ, SCCIS) are pre-invasive stages in the development of squamous cell carcinoma (SCC). METHODS: Immunohistochemical study of cyclin D1, cyclin E, p16(INK4a) and p21(Cip1) (/Waf1) in AK (53 cases), SCCIS (16 cases) and SCC (40 cases), in relation to the type of the lesion and SCC prognostic parameters (grade, diameter and thickness). RESULTS: Diffuse cyclin D1 distribution was more frequent in SCCIS and SCC than in AK (p = 0.03) and similar pattern was observed for p16(INK4a) . For cyclin E, central distribution dominated in SCC compared with the AK (p = 0.001) and SCCIS (p = 0.03). p21(Cip1) (/Waf1) displayed suprabasal distribution more frequently in AK than in SCCIS (p = 0.001) and SCC (p = 0.0004). Semiquantitative assessment showed more positive cells in AK (p = 0.04) and SCCIS (p = 0.04) than in SCC for cyclin E. SCC with diameter over 20 mm and those thicker than 6 mm revealed higher labeling index with p16(INK4a) and p21(Cip1) (/Waf1) , respectively. CONCLUSIONS: Our results suggest different alterations for p16(INK4a) and p21(Cip1) (/Waf1) in AK, SCCIS and SCC. Immunostaining distribution showed closer correlation with the type of the lesion, whereas percentage of positive cells displayed better association with the SCC prognostic parameters.

Cutaneous inguinal scar endosalpingiosis and endometriosis: case report with review of literature.

Endosalpingiosis and endometriosis represent ectopic growth of the fallopian tube epithelium and endometrial glands and stroma, respectively. Cutaneous endometriosis is a well-known entity, most often presented on scars after gynecological procedures. Cutaneous endosalpingiosis, however, appears to be a rare condition, with only 5 cases described in medical literature thus far. The authors report an unusual case of a woman with combined inguinal endosalpingiosis and endometriosis occurring in the cutaneous scar at the site of previously placed surgical drain, 10 years after myomectomy had been performed. The authors also provide an extensive review of medical literature in English regarding cutaneous endosalpingiosis and endometriosis and discuss their clinical, histopathological, and immunohistochemical features.

Giant cystic superficial low-grade fibromyxoid sarcoma.

Low-grade fibromyxoid sarcoma (LGFMS) is a rare type of fibrosarcoma characterized by combination of myxoid and fibrous zones consisted of bland spindled cells. Despite its innocuous histopathologic appearance, LGFMS can produce local recurrence and distant metastasis in the significant number of cases. Tumors are usually situated in deep soft tissues, whereas superficial localization in the dermis and subcutaneous fat is rare. We present a case of 56-year-old man with the huge tumor on the lateral part of the right buttock that had been slowly enlarging over the previous 15 years. Needle aspiration cytology provided only serohemorrhagic fluid with the red blood cells and rare inflammatory elements. Complete surgical excision revealed subcutaneous tumor, measuring 220 × 180 × 130 mm, which was completely cystic, with the residual tumor tissue in the 3- to 25-mm-thick wall. Histopathologic, immunohistochemical, and cytogenetic analysis confirmed LGFMS diagnosis. Long evolution, large size, and the superficial location could cause the repetitive tissue damage and hemorrhage, eventually transforming the tumor into a large cystic mass. In some parts, collagen rosettes composed of eosinophilic core surrounded by a palisade of tumor cells could be seen, occasionally appearing to sprout from the perivascular fibrous coat. Data from the literature regarding cystic appearance as well as the superficial location and the size of LGFMS in relation to the clinical outcome are presented and discussed.

Clinical and pathological features of the giant, invasive basal cell carcinoma of the scalp.

BACKGROUND: The giant, invasive basal cell carcinoma of the scalp is a rare clinical form of this tumor that appears on the skin, but may spread to some of the following structures: soft tissues of the scalp, bones, meninges, and the brain. In literature, so far, it is known as the GBCC. It is caused by aggressive BCC subtypes. METHODS: We will present here a research of clinical and pathological features of 47 pathological specimens in 31 patients where the following features were examined: the dimension of the tumor, the dimension of the tissue segment, tumor area, segmentation area, resection margin width, microscopic resection margin status, tumor invasion level, and the outcome. RESULTS AND CONCLUSIONS: We have concluded that microscopic resection margin dimensions from 1 to 10 mm are safe and that relapse occurrences in giant, invasive BCCs of the scalp depend on microscopic resection margin dimensions, resection margin status, tumor invasion levels, risky occupation, and risky behavior of the patient.

Giant Primary Apocrine Carcinoma of the Frontal Region: Clinical Presentation, Histopathological Features, and Surgical Treatment.

Primary cutaneous apocrine carcinoma (PCAC), a subtype of sweat gland carcinoma, is an extremely rare malignant neoplasm. Distinguishing an apocrine carcinoma from a breast carcinoma metastasis is difficult even for a pathologist. Most arise in regions of high apocrine gland density like the axilla, and rarely on the scalp and eyelid, but they can occur elsewhere on the skin. Primary cutaneous apocrine carcinoma of the scalp is a rare malignancy most often reported in the literature as case reports or small case series. The giant form of primary cutaneous apocrine carcinoma in the frontal region has not been described in the literature, to the best of our knowledge. There are no established protocols for treatment of primary cutaneous apocrine carcinoma. We report a case of a giant primary cutaneous apocrine carcinoma localized in the frontal region. A definitive diagnosis of a primary cutaneous apocrine carcinoma was established by biopsy with microscopic and immunohistochemical analysis. Wide surgical excision and reconstruction with large local transposition flap and split thickness skin grafts for secondary defect were our therapy of choice. Primary cutaneous apocrine carcinoma is a very rare malignancy, and the giant form has not yet been described. Surgical treatment provided the patient with tumor-free status as well as satisfactory aesthetical appearance and quality of life.

Survivin gene promoter -31 G/C polymorphism is associated with Wilms tumor susceptibility in Serbian children.

Survivin, an apoptotic inhibitor, is overexpressed in various types of cancer. Mechanisms of survivin upregulation are still poorly understood, but single nucleotide polymorphisms in the survivin gene promoter have been shown to modulate survivin expression and consequently the risk for some types of cancer. The aim of the present study was to investigate whether survivin promoter -31 G/C and -241 C/T polymorphisms could represent susceptibility factors for Wilms tumor (WT) development in Serbian population. Genotype and allele frequencies for the 2 polymorphisms in survivin promoter have been analyzed by polymerase chain reaction/restriction fragment length polymorphism in 59 WT patients and 82 controls. The frequencies of alleles and genotypes were significantly different between patients and controls for the -31 G/C polymorphism. Individuals with CC and CG genotypes had significantly decreased risk of WT compared with GG individuals (odds ratio 0.26, 95% confidence interval, 0.07-0.96; odds ratio 0.30, 95% confidence interval, 0.15-0.60). There was also a statistically significant difference in genotype frequencies between intermediate and high-risk prognostic groups (P=0.015). The -241 C/T polymorphism did not show association with WT susceptibility. Our findings suggest that the G allele at -31 survivin gene promoter position is associated with a significantly higher cancer risk in Serbian children, with a gene dosage effect.

Pediatric non-Hodgkin lymphoma: a retrospective 14-year experience with Berlin-Frankfurt-Münster (BFM) protocols from a tertiary care hospital in Serbia.

Use of current intensive chemotherapy protocols in pediatric non-Hodgkin lymphoma (NHL) in high-income countries resulted in event-free survival (EFS) rates ranging from 80 to 90%. The results are inferior in less privileged countries with limited resources for medical care. There are no reports about comprehensive data analysis in pediatric NHL in Serbia. A retrospective study was carried out at University Children's Hospital, Belgrade, in children aged less than 18 years diagnosed with non-Hodgkin lymphoma from 1997 to 2011. Fifty-seven children were eligible for analysis. Fourteen were diagnosed with lymphoblastic lymphoma, 38 with mature B-cell NHL (B-NHL), and 5 with anaplastic large-cell lymphoma. Mean age at diagnosis was 9.2 years, with male to female ratio 2.35:1. Children were treated according to Berlin-Frankfurt-Münster (BFM) protocols. With median follow-up of 59.3 months, 5-year probability of EFS was 84.1% for all patients, whereas overall survival was 93%. These results with BFM protocol administration, although inferior to leading international groups, reflect good treatment outcome in our patients. To the best of the authors' knowledge, this article presents the first results regarding treatment and survival of childhood NHL in Serbia.

The use of dermoscopy in distinguishing the histopathological subtypes of basal cell carcinoma: A retrospective, morphological study.

Background The role of dermoscopy in distinguishing the histopathological subtypes of basal cell carcinoma (BCC) is not fully elucidated. Aims To determine the accuracy of dermoscopy in diagnosing different BCC subtypes. Methods The dermoscopic features of 102 histopathologically verified BCCs were studied retrospectively. The tumours were classified as superficial (n=33,32.3%), nodular (n=46,45.1%) and aggressive (n=23,22.6%) BCCs by histopathology. Statistical analysis included Cohen's kappa test, proportion of correlation, measures of diagnostic accuracy, diagnostic odds ratio and the credibility ratio of positive (LR+) and negative (LR-) tests. Results The highest value in all performed tests was seen in superficial BCCs (kappa 0.85; proportion of correlation 93%; diagnostic accuracy 93.1%), good correlation was noted in nodular BCCs (kappa 0.62, proportion of correlation 80%; diagnostic accuracy 80.4%) but dermoscopic correlation with histopathology was low for aggressive BCCs (kappa 0.13; proportion of correlation 79%; diagnostic accuracy 78.4%). Short, fine telangiectasias (83.3%) showed the greatest importance for the diagnosis of superficial BCCs, blue-grey ovoid nests (61.8%) had the highest diagnostic accuracy in nodular BCCs, while arborising vessels (79.4%) was the most significant dermoscopic feature for the diagnosis of aggressive BCCs. Limitations This was a retrospective analysis and included only Caucasian patients from a single centre. Conclusion The highest agreement of dermoscopic features with the histologic type was found in superficial BCCs. We did not find any specific dermoscopic structure that could indicate a diagnosis of aggressive BCC. The presence of relevant dermoscopic features in the evaluated cases was determined by the depth of tumour invasion and not by its histology.

Impact of the COVID-19 Pandemic on Melanoma Diagnosis: Increased Breslow Thickness in Primary Melanomas-A Single Center Experience.

Early melanoma diagnosis plays a key role in ensuring best prognosis with good survival rates. The ongoing global COVID-19 pandemic has greatly impacted global and national healthcare systems, thus making it a real challenge. The aim of this study was to evaluate the impact of the pandemic on diagnostic delay in melanoma patients in Serbia. In this retrospective study, we included patients treated at the university hospital in Serbia's capitol over a period of five years and three months. We compared the prepandemic (01/JAN/17-14/MAR/20) and pandemic periods (15/MAR/20-31/MAR/22) by evaluating patient demographic data, melanoma subtype, Breslow thickness, Clark level, ulceration status, mitotic index rate and pT staging. We observed a significant reduction in the number of diagnosed patients (86.3 vs. 13.7%; p = 0.036), with melanomas having an increased median Breslow thickness (1.80 vs. 3.00; p = 0.010), a higher percentage of Clark IV-V level lesions (44.0% vs. 63.0%; p = 0.009), an increase in median mitotic index rate (2 vs. 5; p < 0.001) and a trend of increase in lesions thicker than 2 mm (37.8% vs. 53.7%; p = 0.026). We believe that this study can be a useful scenario guide for future similar events, highlighting the importance of preventive measures and timely diagnosis for the best patient outcomes.

Molluscum contagiosum arising in melanocytic nevus and in superficial spreading melanoma.

Molluscum contagiosum (MC) is common skin infection caused by molluscum virus. Growth of MC inside melanocytic lesion is extremely rare. We present the case of MC in common melanocytic nevus and the first case of MC in superficial spreading malignant melanoma. Complete destruction of melanocytes and melanoma cells occurred on the site of MC infection. MC virus might be considered as a future candidate for viral oncolysis in cutaneous melanoma patients with advanced disease.

Clear cell myoepithelial carcinoma of the skin. A case report.

Myoepitheliomas are tumors of myoepithelial cells, most frequently diagnosed in the salivary glands. Cutaneous location is very rare, especially for malignant variant. We report a case of recurrent cutaneous myoepithelial carcinoma of the femoral region in a 51-year-old woman. Histologically, the tumor was confined to the dermis and superficial subcutaneous fat tissue, exhibiting typical multinodular pattern. The majority of tumor cells were of clear cell type, although rare epithelioid and spindle cells were also present. Nuclear atypia, mitotic activity of 12 mitoses per 10 microscopic high power fields and Ki-67 labeling index of 20%, as well as three recurrences, corroborated the malignant nature of the tumor. Immunohistochemistry showed positivity for cytokeratin, epithelial membrane antigen, vimentin, S-100 protein and myogenic markers (alpha-smooth muscle actin and muscle-specific actin HHF-35) in keeping with the myoepithelial cell immunophenotype. Staining for CD34, desmin and HMB-45 was negative. Myoepithelial carcinoma should be considered in the differential diagnosis of cutaneous neoplasms composed predominantly of clear cells.

Immunohistochemical analysis of cyclin A expression in Wilms tumor.

BACKGROUND: Cyclin A overexpression is found in a variety of human tumors and correlates with unfavorable outcome. We analyzed immunohistochemical expression of cyclin A in Wilms tumor (WT) in relation to clinicopathological characteristics, preoperative chemotherapy (PrOpChTh), and overall survival (OS). METHODS: This retrospective study involved 43 patients who underwent nephrectomy from January 1996 to October 2010. Tumor stage and histological subtype were determined by revised Societé International d'Oncologie Pediatrique protocol, based on histological components/alterations caused by PrOpChTh, within the prognostic group of low, intermediate and high risk, and with criteria for anaplasia. The regressive/necrotic changes in total tumor mass of primary tumor and the proportion of epithelial, blastemal, and stromal components in the remaining viable tumor tissue were also determined. Cyclin A expression was evaluated by immunohistochemistry using a polyclonal rabbit, antihuman antibody (H-432). RESULTS: Cyclin A overexpression was found in 34.3% of WTs, with higher frequency in tumors with epithelial (31.3%) and blastemal (37.1%) components than those with stromal component (17.7%). Regarding histological type, cyclin A overexpression was found most often in focal anaplasia (100%), stromal (60%), and diffuse anaplastic (66.7) WTs. The overexpression was also more frequent in stages 3 and 4 (77.8% and 66.7%, respectively) compared to tumors in stages 1 and 2 (13.3% and 12.5%, respectively; p = 0.004) in all components, as well as in blastemal component in stages 3 and 4 (77.8% and 66.7%, respectively) vs. stages 1 and 2 (13.3% and 25%, respectively, p = 0.009). Cyclin A overexpression in all components was 66.7% in WTs with metastasis and 31.3% in WTs without metastasis (p = 0.265, Fisher test). Log-rank testing revealed differences of OS regarding stage (p = 0.000), prognostic groups (p = 0.001), and cyclin A expression in blastemal component (p = 0.025). After univariate analysis, tumor stage (p = 0.001), prognostic group (p = 0.004), and cyclin A expression in blastemal component (p = 0.042) were significant prognostic factors for OS; however, after multivariate analysis, none of these factors were confirmed as independent predictors of survival. DISCUSSION: This study showed that cyclin A overexpression might be associated with the development and progression of WT with anaplasia. Also, cyclin A overexpression was more often observed in advanced stages (3 and 4) of WT, in the group of high-risk WTs, and in focal and diffuse anaplasia WTs. There was no relation of cyclin A overexpression and metastatic ability of WT. Although this study has not confirmed the prognostic value of cyclin A overexpression, its association with unfavorable prognosis should be further evaluated.

Insulin-like growth factor-I in wound healing of rat skin.

Growth factors play an important role in orchestrating and enabling the cellular responses required for successful wound healing. In the present study, rat surgical incision was used to investigate insulin-like growth factor-I (IGF-I) expression in skin cells as well as its systemic and cutaneous tissue concentrations during acute phase of wound healing. Thirty two animals were sacrificed at days 2, 3, 5 and 9 after surgery. Eight animals were used as control. Tissue expression of IGF-I in both incisional and periincisional skin areas, as well as in skin of control unwounded animals was determined by immunohistochemistry. Serum and tissue concentrations of IGF-I were measured using RIA. Immunohistochemical analysis revealed enhanced IGF-I immunostaining in the incisional area at day 2 post-wounding. Presence of IGF-I immunoreactivity in the epidermis, as well as in dermal fibroblasts and monocytes within perivascular inflammatory infiltrate suggests its local synthesis. Although serum levels of IGF-I were not altered during wound healing, their tissue contents in the incisional area were significantly increased compared with periincisional area at days 2 and 3 after injury, as well as compared with skin content of unwounded control rats in all examined time points. Obtained results support a paracrine role of IGF-I during the acute phase of wound healing by primary intention in the rat.

Intestinal intussusception due to a pyogenic granuloma.

Pyogenic granuloma (PG), also known as lobular capillary hemangioma, is a benign vascular tumor, most commonly arising on the skin and the oral mucosa. Gastrointestinal localization of PG, except for the oral cavity, is exceptionally rare. We describe a case of ileal PG occurring in a 13-year-old girl, presenting with intestinal obstruction. Histological examination revealed proliferation of capillary-sized vessels, with prominent intravascular component, involving the entire thickness of the intestinal wall. Immunohistochemistry showed positivity for CD31, CD34 and von Willebrand factor, whereas immunostaining for glucose transporter-1 protein (GLUT1) and for human herpes virus 8 (HHV-8) was negative. We suggest that PG should be considered in the differential diagnosis of childhood gastrointestinal polypoid lesions.

Immunohistochemical analysis of gamma catenin in Wilms' tumors.

The aim of our study was to investigate the expression of gamma-catenin in normal kidney and in Wilms' tumor by immunohistochemistry and to correlate the results with tumor stage, histological type, and prognostic group. We investigated 28 cases of Wilms' tumor, 2 Wilms' tumor metastases in lungs, and 1 specimen of normal renal tissue. Expression of gamma-catenin was detected in 14 cases. There was a weak inverse relationship between gamma-catenin expression and tumor stage. Expression of gamma-catenin was detected in various histologic types of Wilms' tumor, but there was no statistically significant correlation, except in cases with diffuse anaplasia that were negative. In 2 metastatic cases and in the case of bilateral Wilms' tumor gamma-catenin immunostaining was not observed Our findings suggest an absence of strong correlation between the loss of gamma-catenin and unfavorable outcome.

Expression of Minichromosome Maintenance Proteins in Actinic Keratosis and Squamous Cell Carcinoma.

Minichromosome maintenance (MCM) proteins are a group of proteins involved in DNA replication and cell-cycle regulation. Because they are associated with DNA through G1 into S phase, MCM proteins are potentially specific indicators of cell proliferation that could be valuable markers of dysplasia, and preinvasive and invasive malignant tumors. To analyze MCM protein expression patterns in actinic keratosis (AK), Bowen disease (BD), and cutaneous squamous cell carcinoma (SCC), we performed immunohistochemical staining of MCM2, -5, and -7 on tissue microarray blocks from 91 AK, 50 BD, and 174 SCC samples. The distribution and semiquantitatively assessed number of positive cells were analyzed in relation to the type of the lesion and the SCC prognostic parameters (grade, diameter, and thickness). Basal expression of all 3 proteins was observed more frequently in AK, whereas the distribution in BD was predominantly diffuse (P<0.001). All 3 proteins showed peripheral distribution in most well-differentiated SCC and diffuse distribution in poorly differentiated tumors (P<0.001). Using the 50% cut-off value, there was a statistically significant difference among AK, BD, and SCC (P<0.001). In addition, all MCM proteins showed highly significant differences (P<0.001) between well-differentiated SCC and both moderately and poorly differentiated SCC. The diffuse distribution and 50% cut-off value of positive cells revealed statistically significant associations of all MCM proteins with SCC thicker than 6 mm. Our results suggest a role for MCM proteins in the progression of in situ keratinocytic lesions and their association with high-risk features in SCC.

Sensitivity and specificity of ex vivo dermatoscopy: a case series.

BACKGROUND: Sensitivity and specificity of ex vivo dermatoscopy (EVD) for malignancy detection of skin tumors is unknown. We sought to assess whether the use of EVD could be a useful adjunct to histopathological diagnosis of pigmented skin tumors, including cases where complete clinical information is inadequate or missing. MATERIALS AND METHODS: EVD was performed on 195 excised, formalin-fixed pigmented skin tumors. RESULTS: Of 183 eligible lesions, 104 (56.8%) were melanocytic and 79 (43.2%) nonmelanocytic. Overall, 54 (29.5%) were malignant: 10 melanomas, 39 basal cell carcinomas, and five squamous cell carcinomas. Ex vivo images were devoid of red color. The following colors were seen: light and dark brown, grey, blue, black, and white. All structures typical for pigmented melanocytic and nonmelanocytic lesions were observed. In malignant nonmelanocytic lesions, diagnostic accuracy and sensitivity for malignant/benign decision was not better when combining visual assessment and EVD but diagnostic specificity improved by 3.0%. For melanoma, combined diagnostics improved diagnostic accuracy, sensitivity, and specificity for 9.6, 30.0, and 7.5%, respectively. CONCLUSION: For dermatopathologists, EVD offers increased specificity for all categories of tumors and increased diagnostic accuracy, sensitivity, and specificity for melanoma. With EVD view, the dermatopathologist can instantly find areas of interest, thus minimizing the possibility for missing a malignant lesion.