Dedifferentiated liposarcoma with leukocytosis. A case report of G-CSF-producing soft-tissue tumors, possible association with undifferentiated liposarcoma lineage

<p>Abstract</p> <p>Background</p> <p>Granulocyte-colony-stimulating factor (G-CSF) functions as a hematopoietic growth factor and it is responsible for leukocytosis. G-CSF-producing tumors associated with leukocytosis include various types of malignancies.</p> <p>Case presentation</p> <p>We report the case of a 72-year-old man with dedifferentiated liposarcoma characterized by dedifferentiated components of malignant fibrous histiocytoma (MFH)-like features in addition to well-differentiated lipoma-like liposarcoma, arising from his upper arm. Preoperative laboratory data showed leukocytosis (103,700/μl). The serum level of G-CSF was also elevated (620 pg/ml [normal, <8 pg/ml]). Nine days after the surgery, the leukocytosis was relieved (WBC; 6,920/μl) and the elevated serum G-CSF level was significantly decreased (G-CSF; 12 pg/ml). One month after the surgery, leukocytosis gradually began to appear again. Three months after the surgery metastatic lung lesions were confirmed, and the patient subsequently died of respiratory problems. In the English literature regarding soft-tissue tumors with leukocytosis, including the current case, we could review a total of 6 cases of liposarcoma with leukocytosis. The subtype of these 6 liposarcoma cases was undifferentiated liposarcoma, comprising dedifferentiated liposarcoma in 4 cases and pleomorphic liposarcoma in 2 cases.</p> <p>Conclusion</p> <p>Since the only other soft-tissue tumor that was associated with leukocytosis was MFH, and since MFH is characterized by the absence of any specific differentiation, we would like to propose a possible association between G-CSF-producing soft-tissue tumors and an undifferentiated liposarcoma lineage, such as dedifferentiated liposarcoma or pleomorphic liposarcoma.</p

p21WAF1/CIP1expression in stage I cutaneous malignant melanoma: its relationship with p53, cell proliferation and survival

The expression of p21, p53 and proliferating cell nuclear antigen (PCNA) was analysed by immunohistochemistry in a consecutive series of 369 clinical stage I cutaneous malignant melanoma patients. Correlation of the detected expression levels with each other, with clinicopathological data and with melanoma survival were statistically evaluated. p21 expression was significantly associated with p53 and PCNA expression levels. In addition, high levels of p53 and PCNA were significantly interrelated. Tumour thickness, recurrent disease, high TNM category and older (≥ 55 years) age at diagnosis were inversely associated with p21 expression. Gender, bleeding, tumour thickness, Clark's level of invasion, TNM category and p53 index were all important predictors of both recurrence-free and overall survival of melanoma. In Cox's multivariate analysis including 164 patients with a complete set of data, only high tumour thickness and bleeding predicted poor recurrence-free survival (P= 0.0042 and 0.0087 respectively) or overall survival (P= 0.0147 and 0.0033 respectively). Even though elevated p21 expression may be associated with more favourable prognosis in clinical stage I cutaneous melanoma, our results suggest that cell cycle regulatory effects of p21 can be overcome by some other and stronger, partly yet unknown, mechanisms. 1999 Cancer Research Campaig

The neuroscience of suicidal behaviors: what can we expect from endophenotype strategies?

Vulnerability to suicidal behavior (SB) is likely mediated by an underlying genetic predisposition interacting with environmental and probable epigenetic factors throughout the lifespan to modify the function of neuronal circuits, thus rendering an individual more likely to engage in a suicidal act. Improving our understanding of the neuroscience underlying SBs, both attempts and completions, at all developmental stages is crucial for more effective preventive treatments and for better identification of vulnerable individuals. Recent studies have characterized SB using an endophenotype strategy, which aims to identify quantitative measures that reflect genetically influenced stable changes in brain function. In addition to aiding in the functional characterization of susceptibility genes, endophenotypic research strategies may have a wider impact in determining vulnerability to SB, as well as the translation of human findings to animal models, and vice versa. Endophenotypes associated with vulnerability to SB include impulsive/aggressive personality traits and disadvantageous decision making. Deficits in realistic risk evaluation represent key processes in vulnerability to SB. Serotonin dysfunction, indicated by neuroendocrine responses and neuroimaging, is also strongly implicated as a potential endophenotype and is linked with impulsive aggression and disadvantageous decision making. Specific endophenotypes may represent heritable markers for the identification of vulnerable patients and may be relevant targets for successful suicide prevention and treatments

Expression Of Androgen Receptor, Epidermal Growth Factor Receptor, And Transforming Growth Factor Alpha In Salivary Duct Carcinoma

Background: Salivary duct carcinoma (SDC) is a rare, highly aggressive neoplasm that primarily affects the major salivary glands. It is a distinct clinicopathological entity characterized by its morphologic resemblance to ductal carcinoma of the breast, a high incidence of regional lymph node metastasis, and distant dissemination. Frequent expression of androgen receptor (AR) but not estrogen receptor or progesterone receptor in SDCs suggests that SDC bears a close immunophenotypic homology with prostatic carcinoma. An AR-mediated autocrine growth pathway consisting of epidermal growth factor receptor (EGFR) and its ligand, transforming growth factor alpha (TGF-alpha), has been implicated in the carcinogenesis of prostatic carcinoma. Androgens, in the presence of AR, mediate their mitogenic effects on prostatic cancer cells by up-regulating the transcriptional and translational activities of EGFR and TGF-alpha. Through an autocrine mode of action, TGF-alpha produced in the tumor cells binds to its receptor, EGFR, which is also ex-pressed by these cells, resulting in a proliferative response. Objective: To investigate whether a TGF-alpha /EGFR autocrine pathway is present in SDCs. Design: Retrospective analysis of the expression of AR, EGFR, and TGF-alpha in 12 SDCs. Setting: An academic medical center. Results: Salivary duct carcinoma expresses AR, TGF-alpha, and EGFR in 11 (92%), 8 (67%), and 11 (92%) of 12 cases, respectively. Conclusion: An AR-mediated TGF-alpha /EGFR autocrine pathway may be implicated in the tumorigenesis of SDC.Wo