Zsolt Orosz

WT1 expression in angiogenic tumours of the skin

Aims : To determine the expression of WT1 in endothelial proliferations and tumours. Endothelial cells are derived from angioblasts which differentiate into bone marrow stem cells (BMSC). BMSC are characterized by the constitutive expression of the WT1 gene and we have postulated that its expression may be maintained during the differentiation of angioblasts to endothelial cells.

The role of boost irradiation in the conservative treatment of stage I-II breast cancer

In this article, we review the current status, indication, technical aspects, controversies, and future prospects of boost irradiation after breast conserving surgery (BCS). BCS and radiotherapy (RT) of the conserved breast became widely accepted in the last decades for the treatment of early invasive breast cancer. The standard technique of RT after breast conservation is to treat the whole breast up to a total dose of 45 to 50 Gy. However, there is no consensus among radiation oncologists about the necessity of boost dose to the tumor bed. Generally accepted criteria for identification of high risk subgroups, in which boost is recommended, have not been established yet. Further controversy exists regarding the optimal boost technique (electron vs. brachytherapy), and their impact on local tumor control and cosmesis. Based on the results of numerous retrospective and recently published prospective trials, the European brachytherapy society (GEC-ESTRO), as well as the American Brachytherapy Society has issued their guidelines in these topics. These guidelines will help clinicians in their medical decisions. Some aspects of boost irradiation still remain somewhat controversial. The final results of prospective boost trials with longer follow-up, involving analyses based on pathologically defined subgroups, will clarify these controversies. Preliminary results with recently developed boost techniques (intraoperative RT, CT-image based 3D conformal brachytherapy, and 3D virtual brachytherapy) are promising. However, more experience and longer follow-up are required to define whether these methods might improve local tumor control for breast cancer patients treated with conservative surgery and RT.

Granular Cell Variant of Atypical Fibroxanthoma.

We report a case of atypical fibroxanthoma of the ear in which the dominant part of the tumor has granular cell appearance. Areas identical to conventional atypical fibroxanthoma were present only at the lateral infiltrating borders. Histologically the granular cells resembled those of the classical granular cell tumors but exhibited significant pleomorphism and a high mitotic rate. Immunostains for vimentin, CD68 and NK1/C3 were positive but for S-100, HMB-45, myogenic and epithelial markers were negative. The predominance of the granular cells in an atypical fibroxanthoma supports the concept that a small subset of tumors with granular cell phenotype are of nonneural origin.

Postirradiation Angiosarcoma of the Chest Wall and Breast: Issues of Radiogenic Origin, Diagnosis and Treatment in Two Cases

The authors report two cases of postradiation angiosarcoma (AS) among 5,100 breast cancer patients treated in the period 1980–1994 at the National Institute of Oncology, Budapest. Relevant data in the literature is also reviewed to analyze the questions of radiogenic origin, diagnosis and treatment. Secondary AS occurred in these cases in a previously irradiated field after a 6- and 8-year latency period, respectively. Detailed histopathological and immunohistochemical examinations from the biopsy specimens confirmed the diagnosis as AS. The first patient was treated successfully with radical surgery. The second patient, with unresectable AS, died of rapid local progression within 4 months. The incidence of chest wall and breast AS after radiotherapy was found to be 0.46 per 1,000 in our patient population, which means an estimated odds ratio of 2.9 for secondary AS. Patients treated with radiotherapy for primary breast cancer are at higher risk for developing secondary AS compared to the healthy population. An etiological relationship between radiotherapy and subsequent AS of the chest wall and breast is likely, but still controversial. Initial radical surgery is the only effective treatment for achieving long-term survival. These very rare cases deserve special attention due to the atypical clinical appearance, difficulties of differential diagnosis and poor prognosis.

Heterogenous S-100B Protein Expression Patterns in Malignant Melanoma and Association with Serum Protein Levels

Objective: Serum S-100B is a reliable tumor marker of malignant melanoma, but efficient use is restricted to patients with metastatic disease. Therefore, the aim of our study was to assess serum S-100B levels at different stages of malignant melanoma and to compare these levels with the expression of the S-100B phenotype in primary tumors and lymph node metastases. Methods: Fifty-nine patients were included in this study; serum S-100B protein was measured using an immunoluminometric assay while the expression pattern in the primary tumor was determined by immunohistochemistry using an anti-S-100B monoclonal antibody. Results: Serum S-100B concentrations were significantly elevated in stage III (p = 0.01) patients, with normal levels in stage I–II. The most frequent S-100B protein expression pattern of the melanoma tissue was found to be diffuse staining observed in around half of the cases (52.5%) followed by heterogeneous (30.5%) and focal patterns (17%), being independent of the stage as well as the lymph node involvement. In stage I–II patients, the various staining patterns did not correlate with the serum concentration of the S-100B protein, while in stage III patients with heterogenous or diffuse S-100B staining patterns in tumor tissue, the serum marker concentration was significantly higher (p < 0.05) than in patients with focal staining. Furthermore, S-100B staining of the melanoma tissue also differed (low/negative, medium and strong staining), and serum marker concentrations corresponded to the pattern of the staining intensity. In stage I–II, only strong staining was associated with elevated serum S-100B concentrations while in stage III medium and strong staining was found to be associated with significantly higher serum marker concentrations compared to patients with tumors with low/negative staining (p < 0.05). Conclusions: In malignant melanoma characterized by focal and/or low S-100B staining in the tumor tissue determined by immunohistochemistry, S-100B monitoring in the serum may not suffice to detect disease progression.

Desmoplastic small round cell tumour of the pleura: a case report with unusual follow-up

In 1994 a 19-year-old woman presented with a few weeks history of back ache. Routine chest X-ray and CT examination revealed a lesion originating from the parietal pleura and destroying the ribs. The tumour was resected during thoracotomy. The histological examination raised the possibility of atypical carcinoid tumour. One year later the tumour recurred. After its re-resection, the patient received radiotherapy. Three years after the initial presentation multiple pulmonary metastases developed. The patient was treated with chemotherapy, receiving vincristine, epi-adriamycin and cyclophosphamide in 8 cycles, which resulted in complete remission. Between 1998 and 1999 progressions and partial remissions were observed, while the patient received further cycles of chemotherapy. Histological revision was performed in 1999 and a final diagnosis of desmoplastic small round cell tumour of the pleura was made. Immunohistochemically co-expression of cytokeratin, vimentin, desmin, and NSE was observed. The patient died in June 2000. The whole follow-up period was 76 months. We thought this case to be worth for presentation because this unusual long survival, which was probably due to the aggressive complex anticancer treatment.

Cytogenetic abnormalities of alveolar soft-part sarcomas using interphase fluorescent in situ hybridization: trisomy for chromosome 7 and monosomy for chromosomes 8 and 18 seem to be characteristic of the tumor.

Abstract. Four alveolar soft-part sarcomas were investigated by means of standard immunohistochemistry and interphase cytogenetics to further characterize the immunophenotype and proliferative activity of this tumor. The main goal of this study was to explore the chromosomal changes of this rare soft-tissue sarcoma. One epithelial (KL1), three neurogenic [neuron specific enolase (NSE), PGP 9.5, and S100], and five myogenic (desmin, myoglobin, α-smooth muscle actin, α-sarcomeric actin, and MyoD1) markers were used for the immunophenotypical analysis. Proliferative activity was assessed using the Ki67 index. Twelve (peri)centromeric (1, 3, 4, 6, 7, 8, 10, 12, 15, 17, 18, and X) and one telomeric (17q25-qtel.) chromosomal probes were used for interphase cytogenetic analysis. Three of the cases showed cytoplasmic desmin and/or myoglobin, and one showed smooth muscle actin positivity. All of the four tumors had granular, cytoplasmic, possibly nonspecific MyoD1 and sarcomeric actin positivity. Two of the tumors were positive for vimentin, four gave focal and weak staining with neurogenic markers (four of four NSE, one of four S100, and four of four PGP 9.5), but none of them was positive with KL1. Alveolar soft-part sarcomas may show myogenic immunophenotype in a number of cases, which supports myogenic differentiation. Fluorescent in situ hybridization using alpha satellite chromosomal probes revealed significant alterations in all of the cases. Most frequent and repeated numerical changes, which seem to be characteristic of the neoplasm and may play an important part in its pathogenesis and/or progression, were trisomy 7, monosomy 8 and monosomy 18.

Through the looking glass: primary epithelioid angiosarcoma in the left atrium, a unique site for a rare malignancy.

Malignant cardiac tumours occurring on the left side are vanishingly rare entities. We describe a case of a 73‐year‐old male who underwent surgery for a left‐sided cardiac tumour following initial presentation with transient ischaemic attacks. In addition to the unusual presentation and subsequent metastatic pattern to the femur, the tumours pathological diagnosis was that of an epithelioid variant of an angiosarcoma which has not been previously described in this anatomical location.