Dimitrije Brasanac

Retroperitoneal kaposiform hemangioendothelioma with tufted angioma‐like features in an infant with Kasabach–Merritt syndrome

Kasabach–Merritt syndrome denotes profound thrombocytopenia and coagulopathy in an infant with a vascular tumor. A retroperitoneal vascular tumor with an unusual combination of histopathological features is reported, and compared with vascular lesions described in the reported cases of Kasabach–Merritt syndrome in the literature. A large retroperitoneal tumor that had expanded through the sigmoid mesocolon into the sigmoid colon wall was resected from an 8‐month‐old infant with fully developed Kasabach–Merritt syndrome. Histological examination revealed a combination of venous (cavernous) malformation, kaposiform hemangioendothelioma and tufted angioma‐like areas. Cellular tumor components (especially tufted angioma‐like parts) infiltrated the wall of the sigmoid colon to the submucosal level. Immunohistochemical staining with antibodies to the Ki‐67 antigen and proliferating cell nuclear antigen showed a low proliferative activity, whereas the antiapoptotic bcl‐2 protein was expressed diffusely in tumor cells. This is the first reported case of a vascular tumor with tufted angioma‐like elements found in the retroperitoneum, and the first reported in combin‐ation with kaposiform hemangioendothelioma and venous malformation in the same lesion. Considering the immu‐nohistochemical results and overlapping histological features, it may be considered that tufted angioma and kaposiform hemangioendothelioma represent different growth patterns or stages in the development of a single type of hemangioma.

Cyclin A and β-catenin expression in actinic keratosis, Bowen's disease and invasive squamous cell carcinoma of the skin

Background  Actinic keratosis (AK) has been defined as a precancerous lesion or an early phase in the evolution of squamous cell carcinoma (SCC) and histological changes seen in the individual cells of an AK are indistinguishable from those seen in SCC, which invade the dermis. Cyclin A is an increasingly utilized proliferation marker that has functions in both S phase (DNA replication) and initiation of mitosis, whereas alterations of β‐catenin, the molecule involved in cell–cell adhesion and in signalling transduction, could promote invasive and proliferative capacities of malignant tumours.

Cadherins and integrins in renal cell carcinoma: an immunohistochemical study.

Aims and Background The aim of this study was to determine the expression of cadherins and integrins in renal cell carcinoma (RCC) and their relationship with tumor morphology and TNM status. Methods Cadherin and integrin expression was investigated using an indirect immunoperoxidase technique, applying antibodies to E-, N-, P- and VE-cadherin and to α1, α2, α3, α4, α5, α6 and αv integrin subunits. Correlation of semiquantitatively scored adhesion molecule levels with histopathological parameters (cytology, growth pattern, nuclear grade) and TNM status was performed for 24 RCCs (17 clear cell, 3 granular, 3 spindle cell and 1 chromophobe cell type according to the WHO classification). Results E-cadherin and N-cadherin were present in most cases (88% and 67%, respectively) and were usually coex-pressed. T3 RCCs displayed higher E-cadherin and N-cadherin levels than T1/T2 tumors regardless of tumor grade, suggesting that impairment of their function might exist without actual loss from tumor cells. P-cadherin was found focally in two RCCs only, while VE-cadherin was present on stromal vessel endothelium in five tumors, showing no differences with regard to cell type, growth pattern, tumor grade or TNM status. All integrins were present in the studied RCCs (ranging from 12% for α5 to 79% for α3), including those that are normally absent from adult kidney tissue (α4 and α5). Tumors of higher grade showed increased αv and decreased α6 levels, while RCCs with metastases less often showed diffuse α3 presence and never expressed α5 integrin. Conclusions Our results suggest that the level of expression of N-cadherin and some integrins (most notably α3, α6, and α5) is associated with the capacity of RCC for local and distant spread, regardless of tumor grade.

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.

Primary cutaneous carcinosarcoma: case report with expanded immunohistochemical analysis

An 83‐year‐old woman presented with a nodular, eroded tumor on the skin between the nose and the upper lip of 18 months’ duration. There were no palpable lymph nodes and no infiltrates on chest radiography. Complete surgical excision showed a tumor measuring 65 × 40 × 30 mm. On histopathologic examination, it was composed of typical basal cell carcinoma (BCC) nodules and large sheets of oval or short spindle cells ( Fig. 1a ), with vesicular nuclei, distinct nucleoli, moderate pleomorphism, and pronounced mitotic activity (more than 40 mitoses/10 high‐power fields). In parts abutting the upper lip, BCC nodules were found in the muscle layer, but the small salivary glands were uninvolved ( Fig. 1b ). Immunohistochemical analysis ( Table 1 ) revealed a cytokeratin (CK)‐positive, Ber‐EP4‐positive, and vimentin‐negative BCC component ( Fig. 2a ), and a vimentin‐positive, CK‐negative sarcomatous component ( Fig. 2b ). In addition, mesenchymal tumor components were focally positive for smooth muscle actin (SMA). The BCC component showed irregular reaction with CK7, which stained some lobules and parts of individual nests ( Fig. 2c ). The final diagnosis was primary cutaneous carcinosarcoma. At the last visit, 3 months after operation, no signs of recurrence or metastatic spread were observed. Additional immunohistochemical analyses showed preserved membranous β‐catenin staining in the BCC component, without nuclear reaction in the mesenchymal component. The labeling index (LI) is expressed as the percentage of positive cells, and is calculated from the number of positive tumor cells divided by the total number of tumor cells counted (minimum 300 cells) in the areas with most pronounced immunopositivity. Counting was performed on images taken from microscopic high‐power fields with an Olympus DP70 digital camera (Olympus Corporation, Tokyo, Japan). The program analySYS (Soft Imaging System, Munster, Germany) was used, with the screen grid and the manual touch‐count method. The LI values of Ki‐67 and telomerase reverse transcriptase (hTERT) were higher in the sarcomatous component. hTERT displayed enhanced nucleolar localization and diffuse staining of mitotic cells. Histone deacetylase 1 (HDAC1) was expressed in a smaller percentage of cells than HDAC2, with a higher LI in the sarcomatous component. HDAC2 was the only marker analyzed that stained more cells in the BCC component ( Fig. 2d ).

Epidermotropic metastases from breast carcinoma showing different clinical and histopathological features on the trunk and on the scalp in a single patient.

A 54‐year‐old female presented with the cutaneous metastases of the breast carcinoma that produced combination of pigmented zosteriform eruption on the trunk and eroded plaque on the scalp, 13 years after radical mastectomy. Histologically, zosteriform lesions displayed prominent infiltration of the epidermis in nesting or linear pattern by neoplastic cells with focal formation of intraepidermal and subepidermal vesicles due to discohesion of tumor cells and dermal edema. Examination of scalp plaque revealed ulcerations and infiltration of the epidermis with scattered basal and suprabasal malignant cells in pagetoid fashion. Immunohistochemically, tumor cells were cytokeratin 7‐ and estrogen receptor‐positive and cytokeratin 20 negative. HMB‐45 and Melan‐A‐stained numerous dendritic melanocytes intermingled with intraepidermal and superficial dermal tumor cells in the trunk lesion, whereas on the scalp, only occasional melanocytes surrounding intraepidermal carcinomatous cells were identified. Our case described, to our knowledge, so far unreported combination of individually rare, clinical and histological patterns of cutaneous metastases from breast carcinoma in a single patient.

Congenital self-healing histiocytosis presenting as blueberry muffin baby: a case report and literature review.

Congenital self-healing Langerhans cell histiocytosis (CSHLCH), also called as Hashimoto-Pritzker disease, is a rare, benign variant of histiocytosis. Despite the initial dramatic clinical presentation, affected infants are otherwise healthy and skin lesions disappear spontaneously within several weeks to months. We present a case of CSHLCH presenting as blueberry muffin baby. The lesions appeared in the first week of life and lasted 6 months. The follow-up period was 24 months, without any signs of relapse. At the pediatric dermatology unit of our clinic, during the last 20 years, we had 10 children with Langerhans cell histiocytosis and among them only one with CSHLCH. In the literature, we found only 5 newborns with Langerhans cell histiocytosis presenting as blueberry muffin baby, among them only 4 with self-healing CSHLCH. The early recognition of CSHLCH may spare children from redundant and potentially toxic systemic treatment.

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 (α‐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.

Changes in common melanocytic naevi after intense sun exposure: digital dermoscopic study with a 1‐year follow‐up

Background.  Exposure to ultraviolet (UV) radiation induces acute changes in common melanocytic naevi (CMN).

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 Childrens 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.