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Granulocytic sarcoma presenting as tumors of the cervix.

BACKGROUND: Granulocytic sarcoma of the cervix, leading to the diagnosis of acute myelogenous leukemia (AML), is a rare event. CASE: A 33-year-old woman presented with vaginal bleeding, pain, and a large pelvic mass involving the cervix, extending bilaterally to the pelvic side walls. A biopsy of the cervix revealed granulocytic sarcoma, and a subsequent bone marrow biopsy confirmed the diagnosis of AML. RESULTS: The majority of patients with cervical granulocytic sarcoma present with vaginal bleeding, sometimes with abdominal pain and other systemic symptoms. The overall 2-year survival rates for all patients with granulocytic sarcoma in the literature is 6%, and none of the patients lived 5 years. CONCLUSION: Granulocytic sarcoma of the cervix is rare. Awareness of this entity will allow earlier diagnosis and appropriate treatment.

Adult↗

Conservative management of a myxoid endometrial stromal sarcoma in a 16-year-old nulliparous woman.

BACKGROUND: Sarcomas comprise less than 1% of all gynecological cancers and 2% to 5% of all uterine malignancies, of which endometrial stromal sarcoma accounts for approximately 15%. Surgery is fundamental in sarcoma management and a total hysterectomy is performed in the majority of cases. CASE: Presented is a case of low-grade myxoid endometrial stromal sarcoma in a nulliparous adolescent female managed by local resection and uterine reconstruction. CONCLUSION: In selected cases, the initial management of a localized and well defined low-grade endometrial stromal sarcoma could potentially be conservative (uterine-sparing) surgical resection.

Adolescent↗

[Two HHV8-related illnesses in a HIV-negative patient: Kaposi's sarcoma and multicentric Castleman's disease. Response to treatment with Rituximab and CHOP].

Human herpes virus 8 (HHV8) was discovered in 1994 in the biopsy of a Kaposi's sarcoma in a patient with AIDS. Since then it has been identified in all variants of Kaposi's sarcoma and in another two rare disorders: multicentric Castleman's disease and primary body-cavity based lymphomas. The case discusses a 68 year old, HIV-negative male patient, presenting Kaposi's sarcoma for one year and being monitored by dermatology, who presented for weakness, anorexia and fever. On examination, he was found to have adenitis of the lymph nodes in his neck, underarm and groin. A biopsy on one of the swellings led to findings characteristic of multicentric plasma cell variant Castleman's disease. Blood tests for HHV8 and HIV were carried out, resulting positive and negative respectively (IgG anti-HHV8 positive, title 1/640, indirect immunofluorescence). PCR amplification showed HHV8 in peripheral blood. Patient received 8 cycles of CHOP and rituximab, leading to complete disappearance of the adenitis and general symptoms, with no worsening of his Kaposi's sarcoma. Patient remained in complete remission for 10 months after treatment. This paper discusses the case of a HIV-, HHV8+ patient, diagnosed with classic Kaposi's sarcoma, who developed multicentric plasma cell variant Castleman's disease. The coincidence of two or more HHV8-related illnesses in a HIV-negative patient has rarely been described in medical literature. Treatment with rituximab combined with CHOP chemotherapy was effective in this case, and no worsening of the patient's KS was observed.

Aged↗

Pulmonary Kaposi's sarcoma: clinical findings and results of therapy.

PURPOSE: Kaposi's sarcoma occurs commonly in patients with the acquired immunodeficiency syndrome (AIDS). Kaposi's sarcoma may remain localized or disseminate to involve visceral organs such as the lungs. Disseminated pulmonary involvement, when it occurs, is often fatal. Effective therapy may improve survival in such patients. We herein report on 20 patients with disseminated pulmonary Kaposi's sarcoma treated with cytotoxic chemotherapy. PATIENTS AND METHODS: Twenty previously untreated patients with pulmonary Kaposi's sarcoma were identified. All were treated with cytotoxic chemotherapy consisting of either Adriamycin alone, a combination of Adriamycin, bleomycin, and vincristine (ABV), or bleomycin and vincristine (BV). The response to therapy and factors affecting prognosis were analyzed retrospectively. RESULTS: Twelve (60%) patients showed a favorable response to therapy. The median survival from the initiation of chemotherapy for the 12 responders was 10 months (range: three to 31 + months) versus six months (range: one to 17+ months) for the non-responders. Eleven of the patients showing a response received ABV or BV combination chemotherapy (p = 0.004). Survival was shortened by the presence of either pleural effusion (p = 0.002), T4 lymphopenia of less than 100/mm3 (p = 0.03), or both at study entry. CONCLUSIONS: In patients with pulmonary Kaposi's sarcoma, combination chemotherapy consisting of ABV or BV is associated with dramatic clinical and functional improvement. The median survival of 10 months demonstrates the value of combination chemotherapy in this group of patients.

Adult↗

Translocation of chromosomes 11 and 22 in choroidal metastatic Ewing sarcoma detected by fluorescent in situ hybridization.

PURPOSE: To describe a patient with metastasis of Ewing sarcoma to the choroid and the molecular genetics of the tumor. METHODS: A 26-year-old woman with metastatic Ewing sarcoma developed large choroidal masses in the left eye and died 2 months later. Autopsy of the eyes was performed. Dual-color fluorescent in situ hybridization was used to detect genetic alteration in the ocular tumor with EWS and FLI-1 probes. RESULTS: Histopathology confirmed choroidal metastatic Ewing sarcoma. Molecular analysis showed chromosomal translocation t(11;22)(q24;q12) or EWS/FLI-1 rearrangement in the malignant cells of the eye. CONCLUSIONS: Ewing sarcoma can rarely metastasize to the uvea. Molecular detection of the t(11;22)(q24;q12) translocation in Ewing sarcoma is valuable in the differential diagnosis of small round cell tumors.

Adult↗

E-cadherin gene mutations frequently occur in synovial sarcoma as a determinant of histological features.

Synovial sarcoma is a mesenchymal tumor that has an epithelial character and two major histological subtypes, the biphasic type and the monophasic fibrous type. However, the mechanisms involved in its epithelial differentiation are unknown, and furthermore, the determinants for histological subtype in synovial sarcoma remain unclear. In this study, we immunohistochemically examined E-cadherin expression and screened for genetic alterations in the E-cadherin gene from exon 4 to exon 9 in 49 cases of synovial sarcoma. In addition, we also examined the mRNA expressions of E-cadherin and Snail, a direct repressor of E-cadherin gene expression, by reverse transcriptase-polymerase chain reaction in 20 samples of frozen material. Immunohistochemical E-cadherin membranous expression was observed in 12 cases (24.5%), and was predominant in biphasic tumors. Single-strand conformation polymorphism analysis followed by DNA direct sequencing revealed 15 missense E-cadherin mutations in 12 cases (24.5%: monophasic, 11 of 42; biphasic, 1 of 6; poorly, 0 of 1) and 7 silent mutations (14.3%) in 7 cases. Ten of the 12 cases with E-cadherin missense mutations did not show E-cadherin membranous expression. Reverse transcriptase-polymerase chain reaction demonstrated E-cadherin and Snail mRNA expressions in 14 cases (70%) and in all cases, respectively. E-cadherin gene expression was inactivated by missense mutations in three of the eight cases (37.5%) of monophasic fibrous tumors that showed E-cadherin mRNA expressions. The E-cadherin gene was potentially inactivated in a significant number of synovial sarcomas. E-cadherin dysfunction because of its mutation in the central region of the molecule was associated with its decreased immunohistochemical expression and histological fibroblastic and spindle-shaped features of monophasic tumors. Thus, E-cadherin gene mutation may be one of the determinants of histological subtype in synovial sarcoma.

Adolescent↗

Radiation-induced breast sarcoma.

BACKGROUND: The purpose of this study was to examine the presentation, treatment, and prognosis of patients with radiation-induced sarcomas after adjuvant radiotherapy for breast cancer. METHODS: This was a retrospective review from 1975 to 2001 of patients who presented with a sarcoma in an irradiated field after surgical treatment for breast cancer. RESULTS: Thirty-four women were included. Six had undergone breast-conserving therapy and 28 had mastectomy for primary breast carcinoma. All patients received postoperative radiation. The mean time to diagnosis of sarcoma was 152 months (range 40 to 372). Twenty-three of 34 patients (68%) had recurrence of the sarcoma after resection, and 22 patients (65%) died of their disease. Patients with no evidence of disease at follow-up had a mean tumor size of 4.2 cm +/- 0.7 (n = 6), compared with 8.1 cm +/- 1.2 (n = 10) for patients who died of their disease (P = 0.030). CONCLUSIONS: Radiation-induced sarcoma is a late complication of definitive treatment for breast carcinoma. The prognosis of such patients is poor, with two thirds dying of their disease. In the present series, improved survival was associated with smaller tumor size at presentation.

Adult↗

Soft tissue sarcomas of the head and neck in adults.

We reviewed the clinical records and pathologic material of 176 adults with primary soft tissue sarcomas treated at Memorial Sloan-Kettering Cancer Center between 1950 and 1985. Seventy-two patients (41%) had low-grade sarcomas and 104 (59%) had high-grade sarcomas. All but 18 patients underwent some form of excision as initial therapy. Adjuvant radiotherapy and chemotherapy combined with surgical excision showed no significant effect. A significantly increased risk of treatment failure was associated with large tumor size, positive surgical margins, bone involvement, local recurrence, metastatic spread, and high histologic grade. Except for recurrence, the p value by univariate analysis in the log-rank test for comparison of survival according to these clinical and pathologic characteristics was p less than 0.0001. Although the overall survival was 75% at 2 years, 55% at 5 years, and 46% at 10 years, only 20% of the patients with high-grade sarcomas were alive 10 years after treatment. Most patients with rhabdomyosarcoma, high-grade peripheral nerve tumor, and high-grade fibrous histiocytoma and all patients with high-grade angiosarcoma died of disease less than 5 years after diagnosis. New therapeutic strategies are needed to improve the survival of adult patients with high-grade soft tissue sarcomas of the head and neck.

Adult↗

Extraskeletal Ewing sarcoma of the diaphragm presenting with hemothorax.

Ewing sarcoma is a relatively uncommon malignant bone neoplasm that usually occurs in children and young adults and involves the major long bones, pelvis, and ribs. Primary diaphragmatic Ewing sarcoma is extremely rare. To the best of our knowledge, only three cases of primary Ewing sarcoma of the diaphragm have been reported. A 12-year-old girl presented spontaneous occurrences of the right hemothorax. After drainage, a roentgenogram film, computed tomography, ultrasonography, and magnetic resonance image showed a giant mass on the right diaphragm. Primary diaphragmatic tumor was resected totally by right posterolateral thoracotomy, and histologically, an extraskeletal Ewing sarcoma was identified. The patient received adjuvant radio-chemotherapy, and there was no evidence of disease 10 months after the operation. Although extremely rare, extraskeletal Ewing sarcoma should be kept in mind in the differential diagnosis of diaphragmatic soft tissue tumors.

Antineoplastic Combined Chemotherapy Protocols↗

Rous sarcoma virus-transformed fibroblasts adhere primarily at discrete protrusions of the ventral membrane called podosomes.

Rous sarcoma virus-transformed BHK cells (RSV/B4-BHK) adhere to a fibronectin-coated substratum primarily at specific dot-shaped sites. Such sites contain actin and vinculin and represent close contacts with the substratum as revealed by interference reflection microscopy. Only a few adhesion plaques and actin filament bundles can be detected in these cells as compared to untransformed parental fibroblasts. In thin sections examined with transmission electron microscopy (TEM) these adhesion sites correspond to short protrusions of the ventral cell surface that contact the substratum at their apical portion. These structures, which may represent cellular feet, are therefore called podosomes. By screening a number of different transformed fibroblasts plated on a fibronectin-coated substratum we find that podosomes are common to mammalian and avian cell lines transformed either by Rous sarcoma virus (RSV) or by Fujinami avian sarcoma virus (FSV), whose oncogenes encode specific tyrosine kinases. Using antibodies reacting with phosphotyrosine in immunofluorescence experiments, we show that phosphotyrosine-containing molecules are concentrated in podosomes. Podosomes are not detected in fibroblasts transformed by other retroviruses (Snyder-Theilen sarcoma virus, Abelson leukemia virus and Kirsten sarcoma virus) or by DNA tumor viruses (polyoma, SV40), indicating that podosome-mediated adhesion in transformed fibroblasts is related to the peculiar properties of some oncoproteins and possibly to their tropism for adhesion systems. Podosomes and adhesion plaques, although similar in cytoskeletal protein composition, have different mechanisms and kinetics of formation. Assembly of podosomes, in fact (i) does not require fetal calf serum (FCS) in the adhesion medium, that is necessary for the organization of adhesion plaques; (ii) does not require protein synthesis; and (iii) is insensitive to the ionophore monensin, that prevents adhesion plaque formation. Moreover, during attachment to fibronectin-coated dishes, podosomes appear in the initial phase (60 min) of attachment, while adhesion plaques require a minimum of 180 min. In conclusion podosomes of RSV- and FSV-transformed fibroblasts represent a phenotypic variant of adhesion structures.

Actins↗

Second malignant neoplasms in children after treatment of soft tissue sarcoma.

Currently, approximately 67% of children diagnosed with cancer can be expected to survive more than 5 years. Among the most significant late effects of cancer therapy is the development of second malignant neoplasm (SMN). This study was performed to identify the factors associated with the development of second malignant neoplasms after treatment for soft tissue sarcomas in childhood. Retrospectively the charts of 20 children who developed second malignant neoplasms after treatment for primary childhood soft tissue sarcoma were reviewed. Presentation, age at diagnosis, tumor histology, extent of tumor, treatment, family histories (when available), and outcome were recorded. The mean age of the patients (10 boys, 10 girls) was 8.5 years of age (range, 1 to 20 years). Most primary tumors were rhabdomyosarcoma (14/20) and occurred in an extremity (10/20). Ninety percent of the patients (18/20) had a complete response to treatment of the primary cancer. Eleven out of 20 received combined chemotherapy and radiation therapy. The most common secondary malignancy was a bone sarcoma (6/20), followed by brain tumors (n = 3), leukemia (n = 2), and other sarcomas (n = 2). Four of the bone sarcomas developed in the field of radiation treatment. Median follow-up was 16 years (range, 1 to 26 years). The median time to development of a SMN was 11.4 years (range, 1.5 to 21 years). Survival after a second malignancy was only 30%. Two patients developed a third malignant neoplasm. The occurrence of a secondary malignancy represents a serious complication of childhood cancer. Certain tumors are related directly to treatment such as osteosarcoma within irradiated fields and secondary leukemias or lymphomas after certain chemotherapy regimens. Combined radiotherapy and chemotherapy may play an additive role in the development of second malignant neoplasms. Genetic factors may predispose affected patients to the development of both primary and secondary malignancies. Close surveillance of children previously treated for childhood cancers is warranted.

Adolescent↗

Spermatic cord sarcoma: outcome, patterns of failure and management.

PURPOSE: We evaluate the outcome, clarify the patterns of failure and suggest treatment strategies for sarcoma in the spermatic cord. MATERIALS AND METHODS: Between 1956 and 1998, 32 patients with spermatic cord sarcoma were treated at M. D. Anderson Cancer Center. A retrospective review of disease outcome, patterns of relapse and patient survival was performed. RESULTS: Histological subtypes of sarcoma were malignant fibrous histiocytoma in 12 patients, leiomyosarcoma in 6, liposarcoma in 8 and other subtypes in 6. All except 2 patients underwent radical orchiectomy with or without additional resection to achieve negative margins. Margins were microscopically negative in 29 cases and positive in 3. There were 3 patients who received adjuvant radiation to the surgical site. With a median followup of 9 years the 10 and 15-year actuarial local control, distant metastasis-free and overall survival rates were 72% and 61%, 85% and 85%, and 63% and 52%, respectively. The major pattern of failure was local recurrence that occurred in 8 of the 12 patients in whom disease relapsed and was the sole site of relapse in 7. Pelvic nodes had relapsed in 2 patients and para-aortic nodes in 1. Hematogenous metastases had developed in 4 patients. Of the 7 cases of disease that recurred locally only 3 were salvaged. No relapse occurred in the 3 patients treated with combined surgery and radiation. CONCLUSIONS: Spermatic cord sarcoma has a high propensity for local recurrence after surgery. Nodal relapse is less frequent than commonly believed. Because of the relatively high local failure rate seen in surgery alone and durable local control noted in 3 patients treated with surgery plus radiotherapy, combined modality treatment should be considered in those with spermatic cord sarcoma who are believed to be at high risk for local failure.

Actuarial Analysis↗

Adult urological sarcoma.

From July 1982 to December 1989, 43 of 1,583 adults (2.7%) with soft tissue sarcoma admitted to the Memorial Sloan-Kettering Cancer Center (MSKCC) had tumors arising from the urinary tract and male genital tract (urological sarcoma). The most common site of origin of the tumor was paratesticular (14 patients), followed by the prostate/seminal vesicle (12), bladder (10) and kidney (7). The most common histological type was leiomyosarcoma (19 patients), followed by rhabdomyosarcoma (14), liposarcoma (5) and 5 other histological sarcoma categories (angiosarcoma, malignant fibrous histiocytoma, mesenchymoma and 2 undifferentiated sarcomas). Most of the tumors were high grade (86%) and more than half (56%) were greater than 5 cm. in diameter. A total of 9 patients (21%) presented with metastatic disease, 8 of whom had rhabdomyosarcoma. Complete resection with negative microscopic margins was possible in 58% of the patients. Actuarial relapse-free survival for all patients at 3 and 5 years was 55% and 40%, respectively. There were no significant differences in survival based on patient age, sex or histological tumor type. Favorable prognostic variables by univariate analysis included tumor diameter less than 5 cm., low histological grade, paratesticular or bladder tumor site and complete surgical resection. Application of the MSKCC sarcoma staging system, which is based on grade, size, depth and presence or absence of metastasis, was useful to predict survival. In our experience patients with stage 3 (high grade, greater than 5 cm., 15 patients) or stage 4 (metastatic disease, 9 patients) had a combined 3-year relapse-free survival rate of only 26% and they should be considered candidates for adjuvant treatment protocols.

Actuarial Analysis↗

Sarcoma of the bladder and prostate.

A retrospective analysis of 30 patients with primary sarcoma of the bladder and prostate is presented. Prognosis seems to be better in adults irrespective of the type of treatment. The survival rate is poor for children with sarcoma of the prostate. Two children were cured of sarcoma of the bladder by a radical operation. Sarcomas of the bladder and prostate are more common in adults more than 50 years old. The type of treatment and the results are reviewed. The place of multimodal treatment in the management of these sarcomas is discussed.

Adolescent↗

Synovial sarcoma: ultrastructural and immunohistochemical features of epithelial differentiation in monophasic and biphasic tumors.

Nineteen synovial sarcomas, six biphasic and 13 monophasic tumors, were examined by light and electron microscopy and immunohistochemically for the presence of the epithelial markers keratin and epithelial membrane antigen (EMA). Ultrastructurally, intercellular spaces with processes are present to varying degrees in the spindle cell component of all synovial sarcomas, and junctional specializations occur in most cases. Tumors of the two types differ in their content of external (basal) lamina, which encloses the epithelial component of all biphasic tumors and is detectable in the spindle cell component of two thirds of them, but is absent from the majority of monophasic tumors. Keratin and EMA were demonstrated in both components of all six biphasic tumors. Of the 13 monophasic tumors, keratin was present in nine, EMA in eight, and at least one epithelial marker in ten. Synovial sarcoma is regarded as a distinctive soft tissue tumor with variable epithelial-like differentiation. The use of electron microscopy can increase the specificity of immunohistochemical studies of soft tissue sarcomas and allow more accurate differentiation of monophasic synovial sarcoma from other spindle cell tumors, particularly those that do not express markers.

Epithelium↗

Intravascular synovial sarcoma.

A biphasic synovial sarcoma occurring in the wall of a pathologically thickened femoral vein was diagnosed in a 34-year-old woman. This sarcoma was resected together with removal of a thrombus. A local recurrence was seen 5 years later, but the patient is alive and well 11 years after the first operation. Immunohistochemical evaluation revealed cytokeratin and epithelial membrane antigen in a portion of the tumor cells, as are typically seen in synovial sarcoma. This case shows that so-called synovial sarcoma may arise in places remote from any joints and that its origin may not be a synovial or perisynovial tissue in all cases. More likely, synovial sarcomas develop from transformed mesenchymal cells, some of which have acquired the epithelial phenotype.

Adult↗

Relevance of cytogenetic and fluorescent in situ hybridization analyses in the clinical assessment of soft tissue sarcoma.

Soft tissue sarcomas are a heterogeneous group of malignant tumors displaying a wide range of clinical presentations, morphological features, and biological behaviors. These characteristics and the recent development of differentiated treatment regimens for the different types of soft tissue sarcomas call for refined histological classification using additional ancillary approaches such as cytogenetic and molecular genetic analyses. We coupled classical cytogenetics and fluorescent in situ hybridization (FISH) on both metaphases and interphase nuclei to show the feasibility of this approach to characterize tumor type-specific chromosome rearrangements in soft tissue sarcomas of different histotype. In 35 cases analyzed, we detected the presence of specific chromosome rearrangements such as t(X;18) in synovial sarcoma (SS), t(12;16) in myxoid liposarcoma (MLS), t(11;22) in peripheral primitive neuroectodermal tumors (pPNET), t(2;13) in alveolar rhabdomyosarcoma (ARMS) and ring chromosomes in dermatofibrosarcoma protuberans (DFSP). In several cases, the presence of these cytogenetic rearrangements was of help for a differential diagnosis. The FISH analysis using painting probes not only confirmed the cytogenetic results but also allowed the identification of tumor-specific chromosome changes in those cases presenting low mitotic index or with poor quality chromosomes. Moreover, in the absence of analysable metaphases, FISH was successfully performed on interphase nuclei. Taken together, these results indicate both the diagnostic and clinical relevance of a molecular cytogenetic analysis in the study of soft tissue sarcomas.

Biomarkers, Tumor↗

Allelic loss on chromosome 22q in epithelioid sarcomas.

Epithelioid sarcomas are soft tissue tumors with an indolent, but potentially aggressive, clinical behavior. Distinction from other benign and malignant entities may be a diagnostic dilemma. In this study, we evaluate the presence of loss of heterozygosity (LOH) of chromosome 22q in tumor DNA from 13 epithelioid sarcomas, four epithelioid angiosarcomas, and two epithelioid hemangioendotheliomas, and investigate its possible role in diagnosis. LOH was detected in 6 of 10 (60%) of the informative epithelioid sarcomas. No allele loss was detected in the informative vascular tumors, three angiosarcomas, and two hemangioendotheliomas. Chromosome 22q carries the locus of a tumor suppressor gene, the neurofibromatosis 2 (NF2) gene, which has been shown to be lost or mutated in some NF2-related tumors, sporadic meningiomas, and vestibular schwannomas, as well as a few other tumors. Our data suggest that a region of chromosome 22q may be the locus of a tumor suppressor gene involved in the tumorigenesis of these neoplasms. Genetic alterations of yet-unknown tumor suppressor genes in this region, or even the NF2 tumor suppressor gene, may play a role in epithelioid sarcomas tumorigenesis. The fact that LOH was only detected in epithelioid sarcomas and not in the vascular tumors studied suggests a possible role for this marker in diagnosis.

Adolescent↗