Primary Pulmonary Synovial Sarcoma during Pregnancy: A Diagnostic and Therapeutic Dilemma

Synovial sarcoma is a rare soft tissue sarcoma that typically arises in the extremities of young adults. We report a case of a 26-year-old pregnant woman with biopsy-proven primary synovial sarcoma of the lung that was treated with chemotherapy with radiographic response. This is only the third documented case of primary pulmonary synovial sarcoma occurring during pregnancy and the first case where chemotherapy was given.Key words: Primary pulmonary synovial sarcoma, Pregnancy, Ifosfamide     

Influence of doxorubicin dose intensity on response and outcome for patients with osteogenic sarcoma and Ewing's sarcoma.

The goal of this study was to use dose-intensity analyses of published Ewing's sarcoma and osteogenic sarcoma trials to determine which agents were most closely associated with a favorable response. The percentage of patients with more than 90% tumor necrosis following neoadjuvant chemotherapy was the end point for analysis of osteogenic sarcoma trials, and disease-free survival and percentage of patients with distant-only relapse were the end points for analysis of Ewing's sarcoma trials. The data were analyzed using logistic regression analysis to circumvent the distortion of univariate analysis resulting from the correlation between doxorubicin dose intensity and the dose intensity of other agents. Our analysis suggests that doxorubicin dose intensity is an important determinant of favorable outcome for both Ewing's sarcoma and osteogenic sarcoma and that the dose intensities of other agents do not contribute as significantly to outcome as does doxorubicin dose intensity. Increasing dactinomycin dose intensity was associated with a poorer outcome in treatment of osteogenic sarcoma and Ewing's sarcoma, most likely resulting from regimens with a higher dactinomycin dose intensity having a lower doxorubicin dose intensity. While our analysis of osteogenic sarcoma trials is consistent with significant activity for cisplatin and high-dose methotrexate (and likely ifosfamide), a rank ordering of the efficacy of these agents when given with doxorubicin in multiagent regimens is not possible. Our analysis illustrates the importance of analyzing the contributions of individual agents to combination chemotherapy regimens. In the design of future clinical trials for osteogenic sarcoma and Ewing's sarcoma, careful attention should be given to optimizing doxorubicin dose intensity in regimens to be tested.     

上皮样肉瘤临床诊治分析

背景与目的:上皮样肉瘤是一种少见的软组织肉瘤, 多表现为肢体远端的结节或溃疡性病变,可通过腱鞘局部播散、淋巴道和血道转移.因其切除后易复发转移、有较高的淋巴结转移率而区别于其他的软组织肉瘤.本文通过分析上皮样肉瘤临床特点,治疗效果,生存情况,预后因素,旨在探讨其治疗方法及预后的影响因素等.方法:回顾我院1999-2007年收治的获得随访的18例上皮样肉瘤,对其临床表现、淋巴结转移、治疗情况、生存率及预后进行分析.结果:上皮样肉瘤5年生存率为41%,局部复发率为44.4%.即使截肢,术后仍有复发.在11例行淋巴结清扫的患者中淋巴结转移率为63.6%.结论:上皮样肉瘤是一种侵袭性较强、淋巴结转移率高、术后易复发的软组织肉瘤,手术应充分考虑切除的广泛性.     

Graduated Systemic Treatment of AIDS-Associated Kaposi Sarcoma

Kaposi sarcoma is a mesenchymal tumor involving blood and lymphatic vessels. It is the most common malignancy in HIV-infected patients and is classified as one of the AIDS-defining diseases. First described as early as 1872, it is only in recent years that deeper insights into the pathogenesis of Kaposi sarcoma have been gained; Kaposi sarcoma represents an extraordinary example of viral oncogenesis and growth control by the immune system. Although the incidence of HIV-related Kaposi sarcoma as the initial manifestation of AIDS has recently decreased, the overall prevalence of the disease remains stable. To date, AIDS-associated Kaposi sarcoma (AIDS-KS) remains a major cause of severe disease complications and fatal outcome in HIV-positive homosexual men. The initial success of systemic interferon-α (IFNα) treatment in AIDS-KS occurred before the identification of the human herpes virus (HHV)-8 (Kaposi sarcoma herpes virus [KSHV]) and in the absence of a coherent view of Kaposi sarcoma pathogenesis. Over the past several years a more comprehensive understanding of how Kaposi sarcoma develops and why the neoplasm occurs at increased virulence in HIV-infected persons has been established. HHV-8 can be found in all types of Kaposi sarcoma, whether related to HIV or not. In the era of highly active antiretroviral therapy (HAART), regression of AIDS-KS has been observed with pure antiretroviral therapeutic regimens. A revival of local therapy of Kaposi sarcoma may occur, if HAART therapy is shown to prevent spreading of Kaposi sarcoma disease. In fact, Kaposi sarcoma is not so much the result of immunodeficiency but the result of immune activation triggered by inflammatory cytokines, which can be partly antagonized by IFNα. In advanced Kaposi sarcoma, conventional chemotherapy used to be a double-edged treatment strategy as it counteracts the reconstitution of the immune system. However, novel agents, for example, pegylated liposomal doxorubicin or daunorubicin, selectively target the tumor with better response rates and less cumulative toxicity than with all other chemotherapies. This article reviews the rationale for and results with graduated systemic therapy of patients with AIDS-KS to yield a more comprehensive treatment approach for this extraordinary malignancy.     

Signal transduction targets in Kaposi's sarcoma

PURPOSE OF REVIEW: AIDS-related Kaposi's sarcoma results from co-infection with HIV and Kaposi's sarcoma herpesvirus/human herpesvirus-8, which leads to the development of an angiogenic-inflammatory state that is critical in the pathogenesis of the condition. Recent discoveries regarding Kaposi's sarcoma herpesvirus/human herpesvirus-8 infection and its activation of signal transduction have led to a greater understanding into Kaposi's sarcoma pathogenesis and have identified potential targets for therapy. RECENT FINDINGS: Kaposi's sarcoma is driven by Kaposi's sarcoma herpesvirus/human herpesvirus-8-specific pathways, which include viral G protein-coupled receptor, viral IL-6, and viral chemokine homologues. In addition, cellular growth/angiogenic pathways such as vascular endothelial growth factor, insulin growth factor, platelet-derived growth factor, angiopoietin and matrix metalloproteinases are 'pirated' by Kaposi's sarcoma herpesvirus/human herpesvirus-8. Recent findings show Kaposi's sarcoma herpesvirus/human herpesvirus-8 specific signaling pathways and pirated pathways to be important therapeutic targets. SUMMARY: Numerous advances have been made recently that expand the understanding of Kaposi's sarcoma pathogenesis. These findings and recent clinical trials of targeted therapy for treatment are a prelude to a shift in the paradigm of how AIDS-related Kaposi's sarcoma is managed.     

Insulin-like growth factor-I receptor activation blocks doxorubicin cytotoxicity in sarcoma cells

More than 80% of patients with extremity sarcoma ultimately develop metastases to pulmonary sites. Doxorubicin alone or in combination with other chemotherapeutic agents may result in partial or complete tumor response for sarcoma pulmonary metastases. Regardless of the response, there has been no proven survival benefit from cytotoxic chemotherapy in the treatment of localized or metastatic soft tissue sarcoma. Insulin-like growth factor-I receptor (IGF-I-R) activation may contribute to resistance to chemotherapy in mesenchymal neoplasia. IGF-I-R activation by its ligand decreases in vitro cytotoxic response of sarcoma to doxorubicin, the most active agent against soft tissue sarcoma in adults. Furthermore, IGF-I-R is frequently overexpressed in soft tissue sarcoma and may predict poor response to traditional chemotherapy. The effect of doxorubicin on a human soft tissue sarcoma cell derived from a dedifferentiated lung metastasis was evaluated using titrated doxorubicin doses with and without exogenous IGF-I (100 ng/ml). Western blot analysis was performed to evaluate levels of phosphorylated IGF-I-R under control and experimental conditions. In vitro proliferation assays were performed. Nuclear activation through IGF-I receptor mediated pathways prior to exposing sarcoma cells to doxorubicin altered the pattern of response to doxorubicin with enhanced mitogenesis (>2-fold) and blunted doxorubicin cytotoxicity (>10% change in IC50). These data suggest that activation of IGF-I receptor in sarcoma cells is a potential mechanism for tumor resistance to doxorubicin. Inhibition of IGF-I receptor activation represents a novel approach to enhance the degree and duration of response to traditional chemotherapy against soft tissue sarcoma.     

Synovial Sarcoma: Laryngopharynx a Challenge

Synovial sarcoma is a rare malignant tumor. It derives from a mesenchymal precursor stem cell that is unrelated to mature synovial tissue. Synovial sarcoma classically affects lower limbs between the ages of 15 and 40 years and the proportion of male-to-female patients is 3:2. It is very rare in the head and neck region especially in laryngopharynx. Till date, only six cases of synovial sarcoma involving laryngopharynx have been reported in the English literature. Painless mass, hoarseness, upper respiratory distress, and dysphagia characterize the original complaints in laryngopharyngeal synovial sarcoma. Because head and neck synovial sarcoma in clinical practice is so uncommon, early diagnosis is difficult and the treatment protocol is unclear. Therefore, every case report should include complete information on presentation and management. Also, long-term prognostic indices need to be evaluated. We hereby report a case of large laryngopharyngeal synovial sarcoma confirmed by histopathology and immunohistochemistry with review of literature.     

Diagnosis of pulmonary Kaposi's sarcoma with fiberoptic bronchoscopy and endobronchial biopsy. A report of five cases

Fiberoptic bronchoscopy is a major tool in the diagnostic evaluation of pulmonary disease in patients with the Acquired Immune Deficiency Syndrome. Multiple opportunistic infections and Kaposi's sarcoma affect the lung in this disorder. In contrast to opportunistic infections, Kaposi's sarcoma is rarely reported to be diagnosed by means of bronchoscopy. This report describes five of seven patients in whom endobronchial lesions consistent with submucosal involvement by the tumor were seen, and Kaposi's sarcoma was diagnosed without complication. Kaposi's sarcoma must be considered in the differential diagnosis of pulmonary disease in patients with a proven extrapulmonary tumor focus, and fiberoptic bronchoscopy is the initial diagnostic procedure of choice. Endobronchial Kaposi's sarcoma may be a marker for parenchymal involvement by the tumor. Diagnosis of endobronchial Kaposi's sarcoma can be an important factor in decisions regarding therapy.     

原发鼻咽部髓系肉瘤缓解后皮肤复发一例并文献复习

目的:提高对原发性髓系肉瘤的认识。方法:回顾性分析安徽医科大学第二附属医院2017年6月诊治的1例首发症状累及鼻咽部的原发性髓系肉瘤患者的临床资料，并复习相关文献。结果:该患者以鼻塞伴耳鸣就诊，接受多次活组织检查及免疫组织化学检查，历经约半年时间确诊髓系肉瘤。采用急性髓系白血病（AML）化疗方案治疗，达到缓解后2年余以新发皮肤包块形式复发，进一步完善骨髓相关检查提示骨髓未受累，仍为孤立性髓系肉瘤，再次行AML化疗方案诱导化疗后皮肤包块完全消失。患者复发后6个月，病情平稳，仍处于随访治疗中。结论:原发鼻咽部髓系肉瘤缺乏特异性，容易被误诊；孤立性髓系肉瘤预后优于AML，诱导化疗缓解后孤立性复发少见，通常较快进展至白血病期；早期和正确诊断对预后十分重要，临床医生应提高对原发性髓系肉瘤的认识。     

Ewing's sarcoma of a lower extremity in an infant. A therapeutic dilemma

A 5.5-month-old infant with Ewing's sarcoma of the left femur is described. The clinical and the pathologic features in this infant are presented in detail, and the dilemma faced in diagnosis and therapy of Ewing's sarcoma in infants is discussed. It is suggested that Ewing's sarcoma in an infant with a lower extremity lesion may be adequately managed without primary amputation.     

Pathogenesis of human immunodeficiency virus-related Kaposi's sarcoma.

Infection with the human immunodeficiency virus-1 is associated with a marked increase in the incidence of Kaposi's sarcoma. Recent studies suggest that the risk of Kaposi's sarcoma in human immunodeficiency virus infection is increased with oral-fecal contact and that a sexually transmitted agent possibly related to human papillomavirus-16 could be involved. Exposure to this or another sexually transmitted agent apparently alters both the morphology and growth regulation of the Kaposi's sarcoma progenitor cells. These changes include the expression of the alpha chain of the interleukin-6 receptor with the acquisition of an interleukin-6-dependent autocrine growth loop. Subsequent perturbation of multiple cytokines during human immunodeficiency virus infection, including Oncostatin-M, interleukin-1 beta and tumor necrosis factor-alpha alters the subsequent growth of Kaposi's sarcoma. These studies suggest that control of cytokine perturbations or the underlying human immunodeficiency virus-1 infection should result in a significant reduction in the rate of growth of acquired immunodeficiency syndrome-related Kaposi's sarcoma.     

子宫肉瘤肿瘤学标记物研究进展

子宫肉瘤迄今为止没有特异件的诊断手段,目前主要依靠组织形态学及免疫组织化学进行诊断,但子宫肉瘤恶性程度高、预后差且无理想的治疗方案.而对子宫肉瘤的肿瘤标记物进行深入研究,对明确诊断、选择治疗方案和判断预后具有重要的指导意义.     

Sarcoma and thyroid disorders: a common etiology?

We have recently observed that many of our sarcoma patients presented also with thyroid disorders. Literature data are almost unavailable on this topic. The relationship between the sarcoma and thyroid disorders is examined. Retrospective analysis of files of patients with sarcoma and clinically overt thyroid disorders was carried out. Of the 375 patients with soft tissue sarcomas (STS) and 235 with bone sarcoma (BS) including small blue round cell tumors (SBRC), 28 patients (4.6%) had an associated significant thyroid disorder. The types of sarcoma were mainly liposarcoma followed by malignant fibrous histiocytoma, leiomyosarcoma and bone sarcoma. The primary sites were mainly limb and trunk. The interval between the diagnosis of the thyroid disorder and the sarcoma varied between -14 years (thyroid first) and +16.5 years (thyroid later) with a median of -0.2 years. Thyroid disorders included goiter, thyroiditis and carcinoma. There are both basic-science and clinical evidence to a possible common pathway that leads to the association between overt thyroid disorders and sarcomas of bone or soft tissues. Oncogene erbA activity is related to thyroid receptors to T3 and to development of sarcoma. Cross talk of the sarcoma oncogene and the erbA might contribute to the development of sarcoma. The thyroid hormone receptor and the highly related viral oncoprotein v-erbA are found exclusively in the nucleus as stable constituents of chromatin. It has been shown that v-erbA can block the spontaneous differentiation in erythroid cells transformed by various retroviral oncogenes. V-erbA can alter the spectrum of neoplasia induced by the v-src oncogene, which causes predominantly sarcomas and erythroblastosis in chicks. The erbA can cooperate with other oncogenes such as v-erbB or with v-fms, v-ras, and c-kit. Cooperation with v-myc may play a role in the development of rhabdomyosarcoma especially in thyroid hormone deficiency state. The possible clinical implications are the need to screen patients with sarcoma to thyroid disorders, and patients with thyroid disorders for malignant diseases.     

Ultrastructural study of 28 cases of Ewing's sarcoma: typical and atypical forms.

The characteristics of 35 round cell sarcomas of bones are analyzed by optical and electron microscopical means, 28 cases of Ewing's sarcoma and 7 cases of malignant lymphomas (reticulum cell sarcoma) being distinguished. The existence of a morphological diversity within the Ewing's sarcoma group allows the authors to differentiate a conventional form of Ewing's sarcoma (21 cases) consisting of principal blastemic cells and secondary degenerative ones (dark cells) from an atypical variant (7 cases of atypical Ewin's sarcoma) whose structure adopts either an immature mesenchymal or histiocytic appearance. The ultrastructure of the atypical Ewing's cells demonstrates variability in size and in the nucleus, which is grooved and possesses prominent nucleoli. In the cytoplasm, in addition to the existence of a variable amount of glycogen, more highly differentiated structures appear when a comparison is made with the principal cells of the conventional Ewing's sarcoma. There exist filaments and mitochondria complexes, desmosomic-like junctions and profiles of endoplasmic reticulum. No transitional forms between the conventional and the atypical variants of Ewing's sarcoma have been observed. According to this analysis, when compared to other bone malignancies, the presence of glycogen as a means for identifying Ewing's sarcoma seems to be of restricted value. No clinical or anatomical differences could be established between either variant of Ewing's sarcoma.     

Kaposi sarcoma as a model of oncogenesis and cancer treatment

Kaposi sarcoma is the most common cancer among HIV-infected individuals and one of the most common cancers in sub-Saharan Africa. Kaposi sarcoma lesions are highly vascularized, and comprised of spindle-shaped tumor cells. Kaposi sarcoma herpesvirus is etiologically linked to Kaposi sarcoma development and encodes genes that contribute to cellular transformation, evasion of apoptosis, aberrant angiogenesis and an inflammatory tumor microenvironment. The study of Kaposi sarcoma herpesvirus-driven malignancies has provided a model of oncogenesis and identified some of the key steps and, therefore, therapeutic targets of Kaposi sarcoma development. However, current Kaposi sarcoma treatments are not specific and rely on reconstitution of the immune system and systemic administration of cytotoxic agents. Recent studies have demonstrated that mechanism-based therapeutics, such as vascular endothelial growth factor A or mammalian target of rapamycin inhibitors, are promising therapeutic approaches bridging basic research with clinical practice.     

Kaposi's sarcoma unrelated to the acquired immunodeficiency syndrome

Kaposi's sarcoma has achieved considerable notoriety in the past decade because of its association with the acquired immunodeficiency syndrome (AIDS). Nonetheless, this neoplasm continues to affect patients who do not have AIDS, and analysis of such cases may provide information that is useful in understanding the pathogenesis and treatment of Kaposi's sarcoma. Recent data indicate that non-AIDS-related Kaposi's sarcoma shows a predilection for individuals with the HLA-DR5 haplotype and that this genetic locus may affect immune function. In addition, other information suggests that infection with cytomegalovirus may represent the "trigger" for oncogenesis in patients with Kaposi's sarcoma. In view of the latter finding, therapies with such antiviral agents as zidovudine may be indicated in cases of non-AIDS-related Kaposi's sarcoma.     

Malignant peripheral neuroectodermal tumor and its necessary distinction from Ewing's sarcoma. A report from the Kiel Pediatric Tumor Registry.

A new classification scheme is proposed for the differential diagnosis of Ewing's sarcoma and malignant peripheral neuroectodermal tumor (MPNT) based on conventional light microscopic and immunohistochemical findings. The presence of Homer-Wright rosettes and/or the expression of at least two neural markers is diagnostic of MPNT Ewing's sarcoma. Ewing's sarcoma was diagnosed in cases lacking Homer-Wright rosettes and expressing no neural marker or only one in immunohistochemistry. Using this "new" approach considerable differences were found between both tumor types. Although most MPNT were located in the thoracopulmonary region, Ewing's sarcoma was located predominantly in the pelvis and extremities. The mean age of MPNT patients was greater than that of Ewing's sarcoma patients. Most importantly, however, was a statistically significant difference in prognosis: disease-free survival in Ewing's sarcoma patients at 7.5 years follow-up was 60% compared with 45% MPNT patients (P = 0.026). The detection of HNK-1 in MPNT indicated a more aggressive biologic behavior, and the expression of protein S-100 appeared to be correlated with a more favorable clinical course.