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PubMed2001

Subgrouping and grading of soft-tissue sarcomas by fine-needle aspiration cytology: a histopathologic correlation study.

To evaluate the accuracy and reproducibility of subgrouping and grading soft-tissue sarcomas by fine-needle aspiration biopsy (FNAB), a blind review was conducted of 84 FNAB specimens from 77 malignant and 7 benign soft-tissue lesions. Cytomorphologic subgroups included 31 spindle-cell, 24 pleomorphic, 11 myxoid, 7 epithelioid/polygonal, 3 small round cell, and 8 nondiagnostic cases. Malignancies included one lymphoma and 41 primary, 15 recurrent, and 20 metastatic soft-tissue sarcomas. Adequacy was defined as a majority of slides with at least 5 clusters of 10 unobscured cells. Five originally false-negative cases were considered nondiagnostic on review. Sarcoma was recognized in 59 of 64 adequate cases (92%) with available histology; however, the specific histopathologic subtype was identified in only 9 cases (14%). Benign myxoid and spindle-cell lesions were difficult to separate from low-grade sarcomas in 4 cases, and a B-cell lymphoma with sclerosis mimicked a low-grade myxoid sarcoma. The assigned cytologic grade accurately reflected the histologic grade in 90% of sarcomas when segregated into high and low grades. Pleomorphic, small round cell, and epithelioid/polygonal subgroups corresponded to high-grade sarcomas in all cases with only minor noncorrelations. Major grading noncorrelations occurred in 50% of myxoid and 9% of spindle-cell sarcomas. Therefore, attention should be given to specimen adequacy, and caution should be exercised when attempting to grade myxoid and spindle-cell sarcomas by FNAB.

Adolescent↗
PubMed1996

Histology, immunohistochemistry, and electron microscopy of small round cell tumors of bone.

Small round cell tumors (SRCTs) of the bone make up a family of primary bone sarcomas with morphologically, biologically, and clinically specific features. Among them, Ewing's sarcoma (ES) is the most common entity, but several varieties such as atypical ES, large cell ES, and ES with neuroectodermal differentiation (peripheral primitive neuroectodermal tumor of the bone or neuroepithelioma of the bone) have been identified recently. Histology and electron microscopy together with the variable expression of several epitopes (as shown by immunohistochemistry, mainly HBA/71 [Mic2 antigen]) provide the basis for characterizing the group within the context of neuroectodermal-derived neoplasms. A number of other ES-like tumors with small round cells, mimicking those previously described, have been characterized; Askin's tumor of the thoracopulmonary region will be considered as an ES similar to those already described, but within a particularly anatomic location. On the other hand, the presence of an endothelial appearance within a poorly differentiated neoplasm may be present in some ES-like SRCTs (atypical ES with endothelial features). The differential diagnosis with other sarcomas defined by small round to spindle cell contours might prove difficult. Particular attention must be paid to small cell osteosarcoma and mesenchymal chondrosarcoma. Likewise, "primitive sarcoma of bone" is considered in this study because it is a very rare neoplasm differing from the formerly discussed types; its pluripotentiality provides this tumor a blastemic character and a multiphenotypic expression. Malignant non-Hodgkin's lymphoma is an unusual presentation when primary to the bone, previous to any other anatomic location. Several subtypes have been considered within a histology that encompasses that seen in lymph nodes.

Bone Neoplasms↗
PubMed1981

Soft tissue sarcomas of childhood: the differential diagnostic dilemma of the small blue cell.

In its histologic features, embryonal rhabdomyosarcoma (RMS), the prototype of malignant soft tissue tumors in childhood, summarizes the problems associated with the diagnosis of this entire group of neoplasms. Many of the tumors that do not fulfill the criteria for RMS have been designated "sarcomas of uncertain histogenesis." The introduction of the concept of a soft tissue equivalent of Ewing's sarcoma may have eased the semantic anxiety without improving our conceptual understanding. It is thought that the embryonal RMS, Ewing's sarcoma, and other are derived from a primitive mesenchymal cell. Another separate category of "small blue cell tumors" are those which presumably originate from the primitive neuroepithelium. Some of the diagnostic terms applied to this category are "neuroepithelioma," "medulloepithelioma," and "peripheral neuroblastoma." Because most of these tumors are hormonally inactive and electron microscopy is not performed, the diagnosis is infrequently considered or proved. The recently described small cell tumor of thoracopulmonary origin is likely a malignant neuroepithelial neoplasm. Hematopoietic tumors, such as non-Hodgkin's malignant lymphomas, granulocytic sarcoma, and malignant histiocytosis, may appear in the soft tissues as the initial manifestation of these system diseases. A final group of malignant soft tissue tumors are the fibrohistiocytic ones with a biphasic pattern of small round cells and spindle cells. It now has become increasingly difficult for the pathologist to satisfy his clinical colleagues with the diagnosis of "undifferentiated malignant tumor" in a child.

Bone Neoplasms↗
PubMed2005

"Undifferentiated" small round cell tumors of the sinonasal tract: differential diagnosis update.

Sinonasal tract neoplasms composed of light microscopically seemingly "undifferentiated" small round cells often generate considerable diagnostic difficulty. Although the careful review of H&E-stained sections remains of critical and central importance in this evaluation, the recent improvements in the immunohistochemical diagnostic armamentarium and molecular diagnostic techniques applicable to paraffin-embedded tissue samples may add diagnostically valuable information. Accordingly, this review will discuss the differential diagnosis of undifferentiated small blue cell tumors of the sinonasal tract based on the light microscopic and clinical features and, as needed, the results of these ancillary studies. Tumors discussed include olfactory neuroblastoma, sinonasal undifferentiated carcinoma, small cell undifferentiated (neuroendocrine) carcinoma, undifferentiated (lymphoepithelioma-like) carcinoma, malignant melanoma, pituitary adenoma, Ewing sarcoma/peripheral neuroectodermal tumor, rhabdomyosarcoma, mesenchymal chondrosarcoma, small cell osteosarcoma, synovial sarcoma, extranodal natural killer/T-cell lymphoma, nasal type, and extramedullary plasmacytoma.

Carcinoma, Small Cell↗
PubMed2006

Adamantinoma-like Ewing's sarcoma with EWS-FLI1 fusion gene: a case report.

Recent studies have advocated the genotypic and phenotypic delineation of a novel Ewing's sarcoma histologic variant showing epithelial features defined as "adamantinoma-like Ewing's sarcoma". We described an 18-year-old girl with a primary small round-cell sarcoma of the right tibia showing polyphenotypic differentiation with epithelioid features. The neoplastic cells had mainly round or oval nuclei with fine chromatin with a portion of epithelial arrangements. The immunohistochemical analysis showed the epithelial markers of cytokeratin 5/6/18, AE1/AE3, and cytokeratin high molecular weight were stained especially in the foci with epithelioid features, as well as MIC2, S100, and NSE. The diagnosis of the lesion was confirmed as Ewing's sarcoma by the presence of the EWS-FLI1 fusion transcript, and could be defined as the so-called "adamantinoma-like Ewing's sarcoma". After wide excision and high-dose chemotherapy with peripheral blood stem cell transfusion, the patient has been well and continuously event-free for 3 years since the initial diagnosis.

Adamantinoma↗
PubMed1993

Surgery in soft tissue sarcomas.

The surgical treatment of soft tissue sarcomas improved in the last decade, with better regional control and an increased number of limb sparing operations, but procedures and criteria of indication are not unified. Moreover, a great discrepancy exists in the incidence rate of local recurrence reported in literature, and also major centres denounce a high rate of local failures. The major predictive parameters of adequate regional control are the size and location of primary lesion, the pathological grading, previous treatments and the quality of surgical margins. Results in terms of regional control of 417 cases treated at our institute in the period 1974-1984 are analysed and discussed. Local failure occurred in 113 cases (27% crude, 31% actuarial risk at 5 years) and has been analysed according to factors which had impact on local failures: pathological grading (low grade 24% local recurrence vs. high grade 35% recurrence, P = 0.05), site (extremity and girdle 26% vs. trunk and head and neck 47%, P = 0.001), previous surgical treatment (32% for lesions recurrent at entry vs. 43% for virgin tumours, P = 0.05), quality of margins (adequate surgery 24% vs. marginal surgery 47%, P < 0.001); intralesional operations are excluded from this series. Histopathology is stratified in four categories that can actually influence the treatment schedule: low grade, spindle cell type high grade, small blue cell, miscellaneous sarcomas of different or unclear histogenesis. The size is detailed in different definitions of small or large, in a site-size relationship which may be useful in surgical practice, with no prognostic purposes. Finally, the adequacy of a surgical treatment is evaluated and discussed by the quality of surgical margins, defined according to the concept of compartment. A surgical indication rationale is, therefore, proposed taking into account the above-mentioned parameters and conclusive points of discussion.

Female↗
PubMed1996

Differential diagnosis of small round cell tumors.

The differential diagnosis of small round cell tumors includes not only the small round cell tumors of infancy and childhood, but a variety of mesenchymal, cutaneous, and lymphoreticular neoplasms that may occur in adults as well as children. Moreover, lesions considered to be the classical small round cell tumors of childhood may occasionally occur in adults, and lesions characteristically seen in adults may at times occur in children. An awareness of the diverse lesions that may present as small round cell tumors is critical to arrive at the correct diagnosis. Immunohistochemical techniques and ultrastructural studies have now become indispensable in the diagnosis of small round cell tumors. With recent developments in cytogenetic and molecular genetic techniques, the pathologist has acquired an even more powerful and precise armamentarium of diagnostic tools. Judicious use of these methods, with knowledge of their significance and limitations, is the responsibility of the pathologist and laboratory coworkers who play a pivotal role in patient care and treatment. The differential diagnosis of small round cell tumors, including adult-type sarcomas, lymphoreticular malignancies, and neuroectodermal tumors of skin and viscera that simulate classical small round cell tumors, is briefly reviewed with this perspective. Specific cytogenetic and molecular markers are covered in addition to the typical immunohistochemical and ultrastructural features of several diverse lesions.

Diagnosis, Differential↗
PubMed1994

High-dose therapy with stem cell support in solid tumors.

We describe some issues of ongoing studies and results in metastatic and high-risk breast cancer. Caution should be used to not over interpret the outcomes of these data given the patient selection. In other tumors with lesser developed studies, such as with ovarian cancer, non seminomatous germ cell tumors (NSGC), childhood sarcoma, melanoma and limited small cell carcinoma, promising outcomes in small phase II studies are identified and proposed or potential studies comparing high-dose therapy to conventional are outlined. High-dose therapy with either peripheral blood stem cell support (PBSC) or autologous bone marrow transplantation (ABMT) in Phase II studies on a diverse array of solid tumors shows exciting promise of long-term, disease-free survival. Comparative studies in early-stage patients are urgently needed to confirm these outcomes.

Breast Neoplasms↗
PubMed1997

LINE-I element insertion at the t(11;22) translocation breakpoint of a desmoplastic small round cell tumor.

A t(11;22)(p13;p12) chromosomal translocation, juxtaposing the Wilms' tumor (WT1) and Ewing's sarcoma (EWS) genes, is the cytogenetic hallmark of desmoplastic small round cell tumor (DSRCT), a primitive multiphenotypic sarcoma arising in serosal tissues. Chimeric transcripts generated by this rearrangement encode an aberrant transcription factor that fuses the 5' region of EWS with a 3' WT1 segment. We describe the insertion of a LINE-I DNA mobile genetic element at the genomic breakpoint of a DSRCT chromosomal translocation. A 480 bp heterologous DNA segment with homology to the LINE-I DNA consensus sequence was located between EWS intron 8 and WT1 exon 8 in the productively rearranged allele. Sequence homology corresponded to the LINE-I ORF-2, which encodes a protein with reverse-transcriptase activity. The heterologous inserted fragment was not evident in the germline of normal tissue from the patient, suggesting that transposition occurred in somatic cells, possibly during the process of chromosomal rearrangement. This case represents the first example of LINE-I DNA transposition at the fusion site of a tumor-associated chromosomal rearrangement.

Alleles↗
PubMed1994

Paranuclear blue inclusions in small cell undifferentiated carcinoma: a diagnostically useful finding demonstrated in fine-needle aspiration biopsy smears.

In a study of bone marrow aspiration smears, Wittchow et al. (Mod Pathol 1992;5:555-558) described a highly characteristic finding, paranuclear blue inclusions (PBIs), found almost exclusively in cases of metastatic small cell undifferentiated carcinoma (SCUC). PBIs are 1-4 microns, light blue, cytoplasmic inclusions best visualized with Romanowsky-type stains. These inclusions are most easily found indenting the nuclei within clusters of closely opposed tumor cells. In the current study air-dried fine-needle aspiration biopsy (FNAB) smears from 146 primary and metastatic small cell and non-small cell adult and childhood malignancies were reviewed. PBIs were found in 28/32 (88%) of SCUC but were observed in only 4/44 (9%) non-small cell carcinomas, 2/21 (9.5%) lymphomas, 1/8 (12.5%) melanomas, 0/14 sarcomas, and 6/27 (22%) small round cell neoplasms. These results suggest that the presence of PBIs in air-dried FNAB smears of adult neoplasms, while not pathognamonic of SCUC, are a diagnostically useful finding. PBIs may be seen in a variety of different childhood small round cell neoplasms which limits their utility in this setting. The recognition of PBIs is most important to the cytologist who may not have access to ancillary studies, such as immunohistochemistry and electron microscopy.

Biopsy, Needle↗
PubMed2003

A tetraspanin-family protein, T-cell acute lymphoblastic leukemia-associated antigen 1, is induced by the Ewing's sarcoma-Wilms' tumor 1 fusion protein of desmoplastic small round-cell tumor.

Recurrent chromosomal translocations in neoplasms often generate hybrid genes that play critical roles in tumorigenesis. Desmoplastic small round-cell tumor (DSRCT) is an aggressive malignancy associated with the chromosomal translocation t(11;22)(p13;q12). This translocation generates a chimeric transcription factor, EWS-WT1, which consists of the transcriptional activation domain of the Ewing's sarcoma (EWS) protein and the DNA binding domain of the Wilms' tumor 1 (WT1) protein. One of the splice variants, EWS-WT1(-KTS) lacks three amino acid residues (Lys-Thr-Ser) in the DNA binding domain and transforms NIH3T3 cells. Therefore, it is likely that aberrant gene expression caused by EWS-WT1(-KTS) is involved in the malignant phenotype of DSRCT. Microarray analysis of 9600 human genes revealed that a gene encoding a tetraspanin-family protein, T-cell acute lymphoblastic leukemia-associated antigen 1 (TALLA-1), was induced in EWS-WT1(-KTS)-expressing cell clones. This induction was EWS-WT1(-KTS)-specific, and more importantly, TALLA-1 protein was expressed in the three independent cases of DSRCT. Tetraspanin-family genes encode transmembrane proteins that regulate various cell processes such as cell adhesion, migration and metastasis. Our findings provide a novel insight into the malignant phenotype of DSRCT, suggesting that TALLA-1 is a useful marker for diagnosis and a potential target for the therapy of DSRCT.

Carcinoma, Small Cell↗
PubMed1998

Chemosensitivity of solid tumor cells in vitro is related to activation of the CD95 system.

We have identified the CD95 system as a key mediator of chemotherapy-induced apoptosis in leukemia and neuroblastoma cells. Here, we report that sensitivity of various solid tumor cell lines for drug-induced cell death corresponds to activation of the CD95 system. Upon drug treatment, strong induction of CD95 ligand (CD95-L) and caspase activity were found in chemosensitive tumor cells (Hodgkin, Ewing's sarcoma, colon carcinoma and small cell lung carcinoma) but not in tumor cells which responded poorly to drug treatment (breast carcinoma and renal cell carcinoma). Blockade of CD95 using F(ab')2 anti-CD95 antibody fragments markedly reduced drug-induced apoptosis, suggesting that drug-triggered apoptosis depended on CD95-L/receptor interaction. Moreover, drug treatment induced CD95 expression, thereby increasing sensitivity for CD95-induced apoptosis. Drug-induced apoptosis critically depended on activation of caspases (ICE/Ced-3-like proteases) since the broad-spectrum inhibitor of caspases zVAD-fmk strongly reduced drug-mediated apoptosis. The prototype substrate of caspases, poly(ADP-ribose) polymerase, was cleaved upon drug treatment, suggesting that CD95-L triggered autocrine/paracrine death via activation of caspases. Our data suggest that chemosensitivity of solid tumor cells depends on intact apoptosis pathways involving activation of the CD95 system and processing of caspases. Our findings may have important implications for new treatment approaches to increase sensitivity and to overcome resistance of solid tumors.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2004

OCT4: a novel biomarker for dysgerminoma of the ovary.

The prognosis and therapy for dysgerminomas are different from those of other ovarian tumor types, making accurate diagnosis imperative for patient care. OCT4 (POU5F1) is a transcription factor involved in the regulation of pluripotency during embryonic development. It can be detected in both pluripotent cells and other early germ cells. This study examines the expression of OCT4 in both dysgerminoma and nondysgerminomatous neoplasms involving the ovary. Formalin-fixed, paraffin-embedded cell blocks of 33 cases of dysgerminoma including 2 cases of gonadoblastoma associated with dysgerminoma and 3 cases of metastatic dysgerminoma, and 111 cases of nondysgerminomatous neoplasms involving the ovary were stained using the antibody against OCT4. All cases of dysgerminomas and gonadoblastomas were positive for OCT4 with strong nuclear staining. More than 90% of dysgerminoma cells in each case showed diffuse strong nuclear staining. In addition, 3 metastatic dysgerminomas also showed uniform strong nuclear staining. All nondysgerminomatous tumors (mature teratoma, 14; yolk sac tumor, 4; Sertoli-Leydig cell tumor, 15; granulosa cell tumor, 22; Brenner tumor, 3; carcinoid tumor, 4; struma ovarii, 2; fibroma, 5; thecoma, 1; serous adenocarcinoma, 5; endometrioid adenocarcinoma, 4; small cell carcinoma, 6; stromal sarcoma, 1; malignant lymphoma, 6; metastatic malignant melanoma, 1; metastatic carcinoid, 2; metastatic small cell carcinoma, 1; and metastatic lobular carcinoma of the breast, 1) were negative for OCT4, except for some cases of clear cell adenocarcinoma of the ovary. Four of 14 clear cell adenocarcinomas showed focal positive nuclear immunoreactivity for OCT4. OCT4 is a sensitive and relatively specific biomarker for the detection of dysgerminoma. It may also be useful in the diagnosis of gonadoblastoma, which contains similar cells and may be associated with dysgerminoma. OCT4 may aid in the detection of small foci of metastatic dygerminoma in extraovarian sites and may also help distinguish dysgerminoma from other primary and metastatic tumors of the ovary.

Adenocarcinoma, Clear Cell↗
PubMed1985

Retrovirus and malignant lymphoma in homosexual men.

We report malignant lymphoma in 27 homosexual men, of whom 22 had high-grade lymphomas (B-cell immunoblastic sarcoma or small non-cleaved lymphoma) and five had low-grade disease. Antibody to human T-cell lymphotropic virus type III (HTLV-III) was present in 13 (87%) of 15 with high-grade lymphoma and in two (40%) of five with low-grade disease. In contrast, only one (9%) of 11 "control" heterosexual patients with high-grade lymphoma had antibody to HTLV-III, while such antibody was found in none of 40 asymptomatic heterosexual controls and in 17 (55%) of 31 asymptomatic homosexual men. Of the homosexual lymphoma patients, 85% presented with disease in extranodal sites, including the central nervous system and rectum, and 81% had reversed T-helper/suppressor ratios. Median survival, despite treatment, is eight months. The acquired immunodeficiency syndrome-related lymphomas in homosexual men are extranodal, high-grade, B-lymphoid tumors, associated with exposure to HTLV-III and unusual clinical characteristics.

Acquired Immunodeficiency Syndrome↗
PubMed2003

Electron microscopy and other ancillary techniques in the diagnosis of small round cell tumors.

The current study disusses a new approach to the group of small round cell tumors (SRCTs) independently of their primary anatomical location. We perform this analysis supported mainly by morphological means and particularly with the help of immunohistochemistry and electron microscopy; the last of which continues to play a decisive role in their differential diagnosis. The microscopical similarity of many of these tumors often makes the diagnosis in routine histology extremely difficult, due to the varying degree of heterogeneity present, and may have important therapeutic and prognostic implications. Thus a correct final diagnosis is mandatory for the clinic. Within the group of tumors that express a dominant or occasional small round cell pattern "SRCT" (neoplasms of the Central Nervous System excluded) are included: Ewing's sarcoma and peripheral neuroectodermal tumor (Es/pPNET) comprising its varieties, neuroblastoma, desmoplastic small round cell tumor, rhabdomyosarcoma, alveolar, solid and embryonal, small cell osteosarcoma, chondrosarcoma, myxoid and mesenchymal, round cell and myxoid liposarcoma, synovial sarcoma (monophasic undiffentiated), primitive malignant peripheral nerve sheath tumor (malignant small cell schwannoma), malignant non-Hogdkin lymphoma, Merkel cell tumor of the skin (small cell carcinoma including neuroendocrine carcinoma). This study discusses in each case not only the histology, supported by immunohistochemistry, but also the main ultrastructural characteristics. We are conscious that in some cases further cytogenetic or molecular biology support may be necessary, when considering the limits of morphology today. Thus, short references on molecular genetics, complementing the structural findings, are given.

Humans↗
PubMedDate not supplied

[Effect of bifolar and chlofiden on DNA synthesis of sarcoma 45 cells and on mitotic activity of rat small intestine epithelium].

Results of the study on the influence of new antitumor preparations chlofiden and bifolar on sarcoma 45 DNA synthesis and on mitotic activity are given. It was shown that bifolar and chlofiden led to inhibition of label incorporation into DNA (3H-thymidine). Inhibition of mitotic activity after injection of both preparations in toxic doses (DL50) was revealed. During injection of the bifolar functional character of changes was established that is mitotic activity of the preparation during injection was restored.

Animals↗