Pleomorphic liposarcoma of bone: a rare primary malignant bone tumour.

BACKGROUND: Liposarcoma is an extremely rare primary bone sarcoma. CASE PRESENTATION: We report a case of primary pleomorphic liposarcoma that arose in an 18 year old male in the metaphysis of the left tibia. Plain radiographs showed a partly sclerotic lesion and MR imaging a heterogeneous tumour predominantly isointense on T1- and high-signal on T2-weighted sequences with focal areas of increased T1 signal that suppressed with fat saturation. PET/CT showed marked FDG uptake (SUV = 17.1) in the primary tumour as well as a metastasis in the right distal femur and multiple small pulmonary metastases. Histologically, the tumour was a pleomorphic liposarcoma containing large tumour cells with vacuolated cytoplasm and hyperchromatic pleomorphic nuclei as well as numerous lipoblasts and scattered brown fat-like cells. Tumour cells strongly expressed FABP4/aP2, a marker of adipocyte differentiation, and UCP1, a marker of brown fat, but not S100. The case was treated with neoadjuvant MAP chemotherapy, resulting in extensive (> 95%) necrosis in the primary tumour and almost complete resolution of the femoral and pulmonary metastases. CONCLUSIONS: Pleomorphic liposarcoma can present as a sclerotic primary malignant bone tumour; markers of adipose differentiation are useful in histological diagnosis and neoadjuvant MAP chemotherapy results in significant tumor necrosis.

Utility of VS38c in the diagnostic and prognostic assessment of osteosarcoma and other bone tumours/tumour-like lesions.

BACKGROUND: VS38c is a monoclonal antibody that recognises a rough endoplasmic reticulum (rER) intracellular antigen termed cytoskeleton-linking membrane protein 63. rER is typically found in viable tumour cells and is abundant in osteosarcoma cells. The aim of this study was to determine the diagnostic and prognostic utility of VS38c in the histological assessment of osteosarcoma and other bone tumours/tumour-like leisons. METHODS: Immunohistochemical staining with VS38c was carried out on formalin-fixed specimens of osteosarcoma (pre/post-chemotherapy) and a wide range of benign and malignant bone lesions. In addition, VS38c staining of cultures of MG63 and Sa0S2 osteosarcoma cell cultures. (±cisplatin and actinomycin D-treatment) was analysed. RESULTS: VS38c strongly stained tumour cells in all low-grade and high-grade osteosarcomas and in undifferentiated sarcomas and high-grade chondrosarcomas. There was little or no VS38c staining of low-grade chondrosarcomas or chordomas and variable staining of Ewing sarcomas. Osteoblasts in benign bone-forming tumours and mononuclear stromal cells in chondroblastomas, giant cell tumours and non-ossifying fibromas strongly stained for VS38c. VS38c staining was absent in cisplatin and actinomycin D treated Sa0S2 and MG63 cells. In specimens of osteosarcoma post-neoadjuvant therapy, VS38c staining was absent in most morphologically necrotic areas of tumor although some cells with pyknotic nuclei stained for VS38c in these areas. Most tumour cells exhibiting atypical nuclear forms were not stained by VS38c. CONCLUSIONS: Our findings show that VS38c is a sensitive but not specific diagnostic marker of osteosarcoma. Staining with VS38c identifies viable osteosarcoma cells, a feature which may be useful in the assessment of percentage tumour necrosis post-neoadjuvant chemotherapy.

Granular cell tumour of the breast: case series and review of the literature.

Granular cell tumours (GCTs) are uncommon rare neoplasms that may occur in any part of the body. Approximately 5-8% of granular cell tumours occur within the breast. Although nearly always benign in behaviour, granular cell tumours of the breast can often mimic breast malignancies both clinically and on the basis of imaging techniques. This article reports five cases of benign granular cell tumours appearing in the breast, mimicking a malignant breast lesion. In addition to reporting the cases, the relevant literature was reviewed.

Impact of repeated bouts of eccentric exercise on sarcolemma disruption in human skeletal muscle.

In animal models, unaccustomed eccentric exercise (EE) has been widely related to muscle fiber membrane (sarcolemma) damage. On the contrary, studies in humans reported that sarcolemma was not susceptible to damage following a single bout of EE. We hypothesized that the single bout of EE used by those studies was not sufficient to induce sarcolemma damage, in humans. In this study we examined muscle biopsies from untrained males who either performed six sets of 15 reps of maximum voluntary eccentric contractions (n=9), for six consecutive days, or served as control-group (n=6). Blood and biopsy samples were obtained one week prior to exercise, immediately after bout 3, and 24h after the last training session. In addition to standard haematoxylin-eosin staining, all biopsies were stained immunohistochemically using antibodies specific for fibronectin and desmin antigens. In the exercise-group, no biopsies taken at pre-exercise or post-exercise level showed evidence of sarcolemma damage as stained by anti-fibronectin antibody in eight of nine subjects. Serum creatine kinase (CK) and lactate dehydrogenase (LDH) activities increased significantly throughout the study despite the lack of sarcolemma damage.We suggest that in humans, repeated bouts of EE do not cause gross sarcolemma damage in the mid-belly of Vastus Lateralis.

Prognosis of patients with local recurrence after mastectomy or conservative surgery for early-stage invasive breast cancer.

Between 1983 and 1987, 1309 women with stage I or II breast cancer underwent mastectomy (n=894) or conservative surgery (CS, n=415). Of these patients, 124 developed an isolated local recurrence (ILR): chest wall, 56 and in-breast, 68. The 10-year actuarial rate of cause-specific survival after treatment for ILR was 52%. On multivariate analysis three independent prognostic factors for the risk of death after ILR were identified: operability of recurrence (operable vs. inoperable, relative risk [RR]: 5.9), age at initial diagnosis (>40 vs. < or = 40 years, RR: 2.2) and time to ILR (>24 vs. < or = 24 months, RR: 2). Initial lymph node stage (negative vs. positive) showed borderline significance (p=0.06), and type of initial surgery (CS vs. mastectomy) and recurrent tumor grade (1-2 vs. 3) were not independent predictors of survival. In the mastectomy group, single surgical scar recurrence with initial node negative stage predicted good prognosis, and the 10-year survival was 85%. In the CS group, the 10-year survival rate was 88% with new primary tumor and 54% with true recurrence (p=0.01), and the type of salvage surgery (mastectomy vs. repeat complete excision) had no significant impact on survival (p=0.2). The majority (n=44) of CS patients developed < or = 2 cm in-breast recurrence, and the 10-year survival was 81% after both salvage excision (n=28) and mastectomy (n=16). The identified unfavorable prognostic factors are pointers of the forthcoming systemic progression. Patients with < or = 2 cm in-breast recurrence might receive a second CS.

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. METHODS AND RESULTS: The expression of WT1 was studied in human umbilical vein-derived (HUVEC) and brain microvascular endothelial cells (HBME) as well as in a Kaposi sarcoma (KS) cell line in vitro. Forty-two human skin biopsy samples of endothelial proliferations and tumours were analysed for the protein expression of WT1 using the monoclonal antibodies for wt-WT1 (6F-H2) and its 17AA+ variant (2C12). WT1 expression was detectable in HUVEC and KS cells and all WT1 splice variants examined (17AA+/- KTS+/-) were detectable in KS cells, while the 17AA+/- and KTS- variants were present in HUVEC. Immunohistochemical analysis of the 42 human skin biopsy samples revealed cytoplasmic WT1 expression using wild-type specific antibody (6FH2) in microvessels, which is maintained during neoangiogenesis (inflammation, haemorrhage, peritumoral angiogenesis). Around one-third of haemangiomas (3/10) and non-HIV-Kaposi sarcomas (7/18) expressed the WT1 protein in the cytoplasm of tumour cells compared with its frequent expression in angiosarcomas (7/8) using the same antibody (6FH2). The nuclear 17AA+ isoform of WT1 was detectable at protein level in a small proportion of KS cases exclusively (3/7). CONCLUSION: Our data suggest that WT1 protein expression is maintained during angiogenesis and malignant transformation of endothelial cells and can be considered as a new endothelial marker.

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.

Dystrophic epidermolysis bullosa complicated by cutaneous squamous cell carcinoma and pulmonary and renal amyloidosis.

A 25-year-old woman with Hallopeau-Siemens recessive dystrophic epidermolysis bullosa had generalized blistering, scarring and milia since birth. In the course of the disease, acral pseudosyndactyly developed, and the patient suffered from corneal erosions, oesophageal strictures, malabsorption, recurrent severe pneumonias and nephrotic syndrome. In addition, she had severe anaemia, sideropaenia, hypocalcaemia, heavy proteinuria and hypoalbuminaemia. A rapidly growing skin squamous cell carcinoma developed on the neck that spread to axillary and cervical lymph nodes. Recurrent hypocalcaemic tetanic convulsions and dyspnoea and a pneumonia refractory to antibiotics led to the premature demise of the patient. Autopsy revealed extensive amyloidosis of the renal, hepatic and splenic tissues. AA type amyloid deposits were detected in the renal glomeruli and in the lung, explaining the patient's unusually severe pulmonary infections. In essence, the patient had severe recessive dystrophic epidermolysis bullosa, complicated by squamous cell carcinoma, recurrent pneumonias and nephrotic syndrome due to secondary amyloidosis of the kidney and lung. The possibility of secondary pulmonary amyloidosis should be considered in severe dystrophic epidermolysis bullosa patients with recurrent pulmonary infections.

Inguinal sentinel lymph node biopsy for staging anal cancer.

BACKGROUND AND AIMS: The optimal treatment of clinically negative inguinal lymph nodes in patients with primary anal cancer has not yet been clearly defined. The presence of metastases in the inguinal lymph nodes is an adverse prognostic factor for anal cancer. In the present study the feasibility of sentinel lymph node biopsy (SLNB) for staging anal cancer was investigated. PATIENTS AND METHODS: From September 1999 to March 2002, 8 patients with biopsy proven primary anal cancer underwent lymphoscintigraphy and dual-agent guided inguinal SLNB for nodal staging before starting multimodality treatment. RESULTS: Inguinal SLNB was successful in all 8 patients (13 groins). A total of 20 hot and blue SLNs (mean 1,5 (1-2) per groins) were removed. In 2 patients (25%) the SLN was positive for metastasis. CONCLUSIONS: Lymphoscintigraphy followed by dual-agent guided inguinal SLNB is technically feasible for staging patients with primary anal cancer. The detection of metastases in the removed sentinel lymph node(s) may alter the treatment and thus may improve the locoregional control and overall survival of these patients.

Molecular pathology of tumor metastasis. I. Predictive pathology.

Millennium reviews of oncology agreed that the last century produced major developments mainly in the management of the primary tumor, but despite all of these results, cancer still remains among the leading causes of death due to the failure of clinical management of disseminated disease. This failure is primarily due to the lack of detailed information on the molecular mechanisms of tumor metastasis. Therefore, one of the hottest fields in experimental oncology is metastasis research, which provides more and more information about the molecular mechanisms. However, this information is fragmented and is not yet exploited in clinical practice. A new field of diagnostic pathology recently emerged, which translates basic research data to diagnostic practice to provide clinically relevant information on the biological potential (in this case metastatic potential) of the malignant tumors. Since tumor cell-extracellular matrix interactions are key features of tumor dissemination, expression of genes responsible for them can define the metastatic potential of malignant tumors. This review summarizes our recent knowledge on the metastatic geno- and phenotype of major human solid tumors: lung, colon, breast, prostate cancers and malignant melanoma.

Syndecan-1 expression in different soft tissue tumours.

BACKGROUND: In vitro studies have suggested that expression of syndecan-1 (CD138) is correlated with morphologic phenotype (epithelioid or spindle) of cultured tumour cells. MATERIALS AND METHODS: Fifty-seven different soft tissue tumours were selected to analyse their syndecan-1 (CD138) reactivity. Immunohistochemical staining of paraffin sections, following a high temperature unmasking technique, was performed. The intensity and the pattern of staining was studied. RESULTS: Cell membrane positivity was observed in epithelioid sarcomas and epithelial elements of synovial sarcomas. GISTs, some malignant epithelioid schwannoma and some fibromatosis showed intracytoplasmatic reaction, while pyogenic granuloma, Kaposi's sarcoma, fibrosarcoma and dermatofibrosarcoma protuberans were negative. CONCLUSION: At first it seemed that the cell membrane positivity of syndecan-1 accompanied true epithelial differentiation in soft tissue sarcomas, but the results further highlighted the non specific nature of this expression. Therefore the heterogeneity in the appearance of syndecan-1 in various soft tissue tumours is not simply associated with the phenotype, suggesting more complex functions.

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.

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 (KLI), three neurogenic [neuron specific enolase (NSE), PGP 9.5, and S100], and five myogenic (desmin, myoglobin, alpha-smooth mnuscle actin, alpha-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 KLI. 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.

[Intraabdominal sclerosing panniculitis--myofibroblast proliferation that can mimic malignancy]. / Intraabdominalis sclerotisáló panniculitis--malignitást utánozni képes myofibroblast-proliferáció.

Intraabdominal sclerosing panniculitis is a fibroinflammatory lesion of the intraabdominal fat tissue of unknown origin. The authors report 4 secondary cases, that were associated with other kind of intestinal pathology. The cases had different clinical manifestation (mesenterial sclerosis leading to bowel obstruction, lesion simulating transmural spread or peritoneal metastasis of colorectal carcinoma, and chance finding associated with ulcerative colitis). They review the literature and summarize the features of the reactive process characterized by a spindle cell proliferation, fibrosis (sclerosis), chronic inflammatory infiltrate and fat necrosis. The immunohistochemical staining pattern of spindle cells favors a myofibroblastic origin. These cells, like cells of many other, but not all myofibroblastic lesions are CD-34 negative. The significance of recognizing the lesion as such is highlighted by the fact that the correct diagnosis has been seldom made without excision of the involved bowel segment. Theoretically surgical excision should be reserved for cases with bowel obstruction, or underlying pathology requiring this intervention. They believe that with awareness of the lesion secondary cases are not as rare as previously thought, although primary cases (those not associated with other intestinal pathology or specific etiologic agents) are only rarely encountered in everyday practice. They share the view that both primary and secondary cases are reactions to noxious agents, but this agent is unknown in primary cases.

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.

Endoscopy and autopsy follow-up of biodegradable oesophageal anastomoses in dogs.

The biofragmentable Anastomosis Ring (BAR) is a mechanical device composed of absorbable material and creates an inverting, atraumatic compressive anastomosis with no foreign material at the anastomotic site after healing. The aim of the present experimental study was to assess the safety of oesophagoscopy in early days after oesophageal anastomoses performed with the BAR and to follow-up the healing of BAR anastomoses by in vivo endoscopy and autopsy examination. Thirty mongrel dogs divided into subgroups according to the time-points of endoscopy and autopsy (4th, 7th, 14th, 28th day) were used. There was no significant difference in the healing of anastomoses performed under or above the tracheal bifurcation. Pleural adhesions helped to cover and seal small subclinical leaks. The mortality was 13.3% (4 dogs) and the overall leakage rate 14.3%. We looked for bleeding, haematoma, erosion, ulceration and granulation tissue in the anastomosis. Due to the high mechanical strength of these anastomoses, oesophagoscopy was a safe, easy and feasible method for follow-up BAR intrathoracic anastomoses, with no significant difference between the number of lesions found with endoscopy as compared to the autopsy data. The overall sensitivity of oesophagoscopy to discover mucosal lesions was 73.1%. Endoscopy had no complications, therefore it is a useful method of follow-up and may help predict the normal or compromised healing of oesophageal anastomoses.

Immunohistochemical features of paragangliomas.

Immunohistochemistry is part of the routine diagnosis of the neuroendocrine tumors. In our study, we included 52 paragangliomas with various localizations by routine histology and immunohistochemistry. In order to increase the diagnostic specificity, a complex immunohistochemistry panel has been performed consisting of Bcl-2, Ki-67, Bax and Pituitary Adenylate Cyclase-Activating Peptide (PACAP), somatostatin, VIP and Calcitonin Gene Related Peptide (CGRP). After heat induced antigen retrieval, the immunostaining was performed by StreptABC using DAB as a chromogen. We were the first to demonstrate the presence of Bax and PACAP in paragangliomas. Some of the used markers are of prognostic value. The relationship between Bcl-2 and Bax is decisive in generating the final response to the input apoptotic signals. The Ki-67 antigen staining has gained wide acceptance in prognostic evaluation of other tumor types. We noted a small number of Ki-67 positive cases, which signifies a low mitotic activity of these tumors and a relatively high number of Bax positivities (32.9%) and the much lower number of Bcl-2 positivities (11.39%), and could explain the benign behaviour of paragangliomas.

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.

Angiolymphoid hyperplasia with eosinophilia: report of a lesion mimicking soft tissue tumor of extremely long duration.

We present a large sized lesion of the right upper arm in which characteristics of the angiolymphoid hyperplasia with eosinophilia (ALHE) intermingled with those of Kimura's disease (KD). The laboratory findings, the prominent vascular proliferation and the features of endothelial cells were suggestive of ALHE. However, the long duration of the disease, the site of involvement, the abundant lymphoid component forming lymph follicles with germinal centers and the fibrosis are features of KD. In agreement with other reports, our case shows that clinicopathologically there is an overlap between ALHE and KD.