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.

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.

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.

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.

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.

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.

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.

Targeted molecular profiling reveals genetic heterogeneity of poromas and porocarcinomas.

The genetic landscape of rare benign tumours and their malignant counterparts is still largely unexplored. While recent work showed that mutant HRAS is present in subsets of poromas and porocarcinomas, a more comprehensive genetic view on these rare adnexal neoplasms is lacking. Using high-coverage next generation sequencing, we investigated the mutational profile of 50 cancer-related genes in 12 cases (six poromas and six porocarcinomas). Non-synonymous mutations were found in two-thirds of both poromas and porocarcinomas. Hotspot HRAS mutations were identified in two poromas (p.G13R and p.Q61R) and one porocarcinoma (p.G13C). While in poromas only few cases showed single mutated genes, porocarcinomas showed greater genetic heterogeneity with up to six mutated genes per case. Recurrent TP53 mutations were found in all porocarcinomas that harboured mutated genes. Non-recurrent mutations in porocarcinomas were found in several additional tumour suppressors (RB1, APC, CDKN2A, and PTEN), and genes implicated in PI3K-AKT and MAPK signalling pathways (ABL1, PDGFRA, PIK3CA, HRAS, and RET). UV-associated mutations were found in TP53, APC, CDKN2A, PTEN, and RET. In conclusion, our study confirms and extends the spectrum of genetic lesions in poromas and porocarcinomas. While poromas exhibited only few mutations, which did not involve TP53, the majority of porocarcinomas harboured UV-mediated mutations in TP53 with some of these cases showing considerable genetic heterogeneity that may be clinically exploitable.

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.

Lymphoblastic lymphomas in children ­ A single-center experience from Serbia.

Introduction: Intensive treatment protocols used for non-Hodgkin lymphoma in children lead to eventfree survival rates ranging from 80% to 90%. However, the results are less successful in developing countries. Lymphoblastic lymphoma (LBL) is the second most frequent type of lymphoma in children, contributing with about one third to all non-Hodgkin lymphoma in childhood. Objective: The aim of the study was to evaluate the results of LBL treatment in University Children's Hospital (UCH), Belgrade. Methods: A retrospective analysis of patient records at UCH from 1997 to 2015 was carried out in patients aged 0­18 years, in whom the diagnosis of LBL had been established. Twenty-two children were included in the analysis. Results: Mean age at diagnosis was 10 years, with preponderance of male patients. All patients were treated according to Berlin-Frankfurt-Münster-based chemotherapy protocols. With median follow-up of 91.5 months, five-year probability of event-free survival was 79.5% for all patients, while overall survival was 81.8%. Conclusion: Our results, although slightly inferior to those of leading international groups, reflect a good treatment outcome in our patients.

Gianotti-Crosti syndrome associated with Ebstein-Barr virus and Parvovirus B-19 coinfection in a male adult: case report and review of the literature.

Gianotti-Crosti syndrome (GCS) is a self-limiting, mostly childhood-appearing, cutaneous eruption with characteristic symmetric areal distribution. The original cases, described by Gianotti in 1955, were associated with hepatitis B virus infection, but other viral and bacterial infections, as well as immunizations, have been implied in etiology of this condition. Adult cases are rare and have been reported almost exclusively in women. We present the case of a 20-year-old Caucasian man who had typical clinical presentation: monomorphic pale, pink-to-flesh - colored or erythematous papules and papulovesicles localized symmetrically over the extensor surfaces of the extremities, buttocks and the face; some lesions were detected on knees, elbows and palms, as well. Laboratory tests revealed slight bilirubin and alanine aminotransaminase elevation. Serology tests demonstrated antibodies against Epstein-Barr virus and parvovirus B-19. Histology of skin biopsy specimens revealed a vesicular dermatitis with perivascular lymphocytic infiltrate. Oral and topical corticosteroids and oral antihistamines led to complete resolution of lesions in 3 weeks. GCS is rare in adults, especially men. To the best of our knowledge, this is the fifth male adult case and the first with Parvovirus B-19 and EBV coinfection.

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 composite hemangioendothelioma: case report and review of published reports.

Composite hemangioendothelioma (CHE) is a rare, locally aggressive, vascular tumor of intermediate-/ low-grade malignancy, and is characterized by varying combinations of benign, low-grade malignant, and malignant vascular components. In cutaneous localization, only 22 cases have been reported so far. A new case of CHE of the gluteal region in a 58-year-old man is described. Microscopically, vascular neoplasm, situated mainly within the deep dermis and the subcutaneous fat tissue, was composed of sinusoidal hemangioma, arteriovenous hemangioma, retiform hemangioendothelioma (RHE), and angiosarcoma. An average number of mitoses within the angiosarcomatous component was 10 per 10 high-power fields. Immunohistochemically, the tumor cells were positive for factor VIII-related antigen, CD34, and CD31 and negative for D2-40 and GLUT-1. Ki-67 labeling index was 21%, 1.2%, and 0% in the areas of angiosarcoma, RHE, and sinusoidal hemangioma, respectively. No recurrent disease was noted 3 months after the surgery. The present case displayed the following features previously undescribed in CHE: a novel component of sinusoidal hemangioma and localization at the gluteal region. We also provide review of clinical, histopathological, and immunohistochemical characteristics of cutaneous CHE from the published cases.

Zygomatic bone metastasis as an initial presentation of hepatocellular carcinoma.

Hepatocellular carcinoma is the most common type of primary liver cancer. It metastasizes via blood or through lymphatic dissemination, most comonly to the lungs, abdominal lymph nodes, and bones. Metastases to the bones of the head and neck region, however, are extremely uncommon. A 70-year-old male was presented with a mass in the left zygomatic region. After the incisional biopsy, the histopathologic and immunohistochemical analysis confirmed a metastasis of hepatocellular carcinoma. An abdominal computerized tomography (CT) scan  revealed a large primary tumor in the right liver lobe. To the best of our knowledge, this is the second case of an isolated zygomatic metastasis as an initial presentation of hepatocellular carcinoma. We also reviewed the literature regarding clinical and histopathologic characteristics of hepatocellular carcinoma that produced metastases to the zygomatic bone and the maxilla.

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.

[Clinical-epidemiologic characteristics of large, invasive basal cell carcinomas of the scalp].

We studied a large, invasive basal cell carcinoma of the scalp in 42 operated patients (53 tumors) of which 26 patients with recurrent and 16 with no recurrence. This is a rare clinical form of this tumor that invades the skin in addition to some or all of the following structure: soft tissue scalp, skull, brain and brain membranes. The literature is known as the Giant basal cell carcinoma according to TNM classification of BCC in pT4 stage. Caused by aggressive subtypes of BCC. Treatment is surgical and involves only large, mutilate surgery and extensive reconstruction. Relapse often occurs. The aim was to analyze clinical and epidemiological characteristics of large, invasive basal cell carcinoma of the scalp, finding the causes of relapse and proposal timely diagnosis. We have concluded that the appearance of tumors in the frontal and pariental region of the scalp is related to the presence of known risk factors, that tumors often penetrate bones and brains resulting in more frequent recurrence in this localization. All tumors were caused by aggressive forms of BCC. Patients in the group with recurrent, previously responded to treatment and had more surgery than patients without recurrence. Treatment-related adverse events occurred in most patients (recurrence and/or death).

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.