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A survey of clusterin and fascin expression in sarcomas and spindle cell neoplasms: strong clusterin immunostaining is highly specific for follicular dendritic cell tumor.

Clusterin, a glycoprotein implicated in many cellular functions including apoptosis, has recently been shown to be strongly expressed in follicular dendritic cell tumors, and to be absent or only weakly expressed in other dendritic cell tumors. Fascin has also been investigated as a potential marker of dendritic cell neoplasms. We evaluated staining for antibodies directed against these two antigens in 202 spindle cell tumors, including cases of follicular dendritic cell tumor (n=14), interdigitating dendritic cell tumor (n=7), leiomyosarcoma (n=17), inflammatory myofibroblastic tumor (n=13), inflammatory pseudotumor (n=2), spindle cell thymoma (n=17), synovial sarcoma (n=11), fibrosarcoma (n=14), liposarcoma (n=27), gastrointestinal stromal tumor (n=13), malignant fibrous histiocytoma (n=18), angiomatoid fibrous histiocytoma (n=4), angiosarcoma (n=10), malignant peripheral nerve sheath tumor (n=8), malignant melanoma (n=16), and spindle cell carcinoma (n=11). Among these spindle cell neoplasms, strong diffuse clusterin staining had an overall specificity of 93% and a sensitivity of 100% for follicular dendritic cell tumor. Clusterin staining was least reliable in distinguishing follicular dendritic cell tumor from spindle cell thymoma or malignant fibrous histiocytoma, but these are entities that usually can be distinguished by clinical and morphologic data. Rare cases of leiomyosarcoma, fibrosarcoma and angiosarcoma may show strong clusterin staining. Fascin staining was very nonspecific among spindle cell tumors and thus does not imply a dendritic cell lineage.

Carrier Proteins↗

Lipoleiomyosarcoma of the mediastinum.

A case is described of a mediastinal soft tissue sarcoma, in a 76-year-old man, characterized microscopically by the intimate combined features of liposarcoma and leiomyosarcoma. The lipomatous component consisted of well differentiated liposarcoma with myxoid areas. The smooth muscle component was characterized by fascicles of spindle cells showing nuclear atypia and scattered mitoses. The spindle cells displayed intense reactivity for alpha smooth muscle actin (ASMA), desmin and vimentin. Differential diagnoses included dedifferentiated liposarcoma, spindle cell liposarcoma, angiomyolipoma and myolipoma. To the best of our knowledge no case of sarcoma in the mediastinum with combined features of liposarcoma and leiomyosarcoma has been reported. The dual lineage differentiation of the lipoleiomyosarcoma may be difficult to identify in small biopsy samples which may not represent the tumor as a whole. Lipoleiomyosarcoma should be included in the differential diagnosis of soft tissue tumors arising in the mediastinum.

Actins↗

Practical application of molecular genetic testing as an aid to the surgical pathologic diagnosis of sarcomas: a prospective study.

The strong correlation of specific reciprocal translocations with individual tumor types and the demonstration that polymerase chain reaction (PCR)-based methods can detect translocations in tissue samples have stimulated interest in the role of molecular genetic testing in diagnostic surgical pathology. To evaluate the clinical utility of PCR-based molecular analysis of soft tissue neoplasms in routine surgical pathology, 131 consecutive soft tissue tumors submitted for molecular genetic testing at a tertiary care teaching hospital were prospectively analyzed over a 36-month period. RT-PCR was used to test tumor RNA for fusion transcripts characteristic of malignant round cell tumors (including Ewing sarcoma/primitive neuroectodermal tumor, desmoplastic small round cell tumor, and alveolar rhabdomyosarcoma), spindle cell tumors (including synovial sarcoma and congenital fibrosarcoma), and fatty tumors (myxoid liposarcoma). DNA sequence analysis was used to confirm the identity of all PCR products, and the PCR results were compared with the histopathologic diagnosis. We found that sufficient RNA for RT-PCR-based testing was recovered from 96% of the 131 cases and the percentage of tumors that tested positive for the associated characteristic fusion transcript was in general agreement with those reported in the literature. DNA sequence analysis of PCR products identified both variant transcripts and spurious PCR products, underscoring the value of product confirmation steps when testing formalin-fixed, paraffin-embedded tissue. Only in rare cases did testing yield a genetic result that was discordant with the histopathologic diagnosis. We conclude that PCR-based testing is a useful adjunct for the diagnosis of malignant small round cell tumors, spindle cell tumors, and other miscellaneous neoplasms in routine surgical pathology practice.

Base Sequence↗

Distribution of steroid hormone receptors in human soft tissue sarcomas.

Sixty-six human soft-tissue sarcoma specimens were assayed for incidence and distribution of steroid hormone receptors. Liposarcomas (43%) and leiomyosarcomas (60%) had a high incidence of estrogen receptor. In contrast, sarcomas of fibrous and synovial tissue origin lacked any detectable receptor for estrogen. Malignant fibrous histiocytoma had the highest incidence of glucocorticoid (66%) and androgen (66%) receptors. The incidence of receptors for estrogen and glucocorticoid was higher in female than in male patients (62% and 38%, respectively). Sucrose density gradients demonstrated 8s-type receptors for both estrogen and glucocorticoid. Data from this study suggest that specific high-affinity cytosolic receptors for steroid hormones are present in human soft tissue sarcoma and that their distribution may depend on the histogenetic origin and the sex of patients.

Adolescent↗

Usefulness of argyrophilic nucleolar organizer staining for predicting prognosis of patients with recurrent soft tissue sarcoma.

Local recurrence of tumor is a common phenomenon in soft tissue sarcoma (STS) and may be accompanied by an increase in malignant potential. In the present study, an increase of proliferative activity in recurrent tumors compared to primary tumors was observed using a silver stain for nucleolar organizer regions (AgNOR), and its implication for predicting prognosis is assessed. 44 patients with STS showing local tumor recurrence were selected. Local recurrence was defined as new tumor growth more than 2 months after the initial surgery in the same region where the primary tumor occurred. All patients received surgery, followed in 11 patients by adjuvant radiotherapy and/or chemotherapy. The histologic subtype was malignant fibrous histiocytoma in 22 cases, synovial sarcoma in 5, leiomyosarcoma in 4, liposarcoma in 3, malignant schwannoma in 3, and others in 7. The interval between initial surgery and local recurrence ranged from 2 to 72 months. No patients changed from one histological subtype to another. Histological changes included an increase in mitosis, cellularity, and sclerosis in 43.2, 31.8, and 27.3%, respectively. The AgNOR count (mean +/- SD) in recurrent tumors (7.22 +/- 2.59) was significantly higher than that in primary tumors (5.58 +/- 2.28; p < 0.0057), clearly showing a tendency for an increase in proliferative activity during recurrence. The 5-year survival rate of patients with a marked increase (> 4) in AgNOR count (16.7%) was worse than with minor to moderate increases (60.0%; p < 0.02). Marked AgNOR increase was more frequently observed in the tumors located in the head and neck and retroperitoneum (40%) than in other sites (9%). Irrespective of the primary site of tumors, a marked AgNOR increase resulted in an unfavorable prognosis. Multivariate analysis of change in histologic factors including AgNOR, cellularity, mitotic counts, pleomorphism, myxoid change, necrosis, sclerosis, and tumor size showed that increase of AgNOR counts was significant (p < 0.05). The present findings suggest that AgNOR counts can be used as a prognostic factor in recurrent STS.

Adult↗

Immunization by particle-mediated transfer of the granulocyte-macrophage colony-stimulating factor gene into autologous tumor cells in melanoma or sarcoma patients: report of a phase I/IB study.

The primary objective of this phase I study was to determine the safety of an autologous tumor vaccine given by intradermal injection of lethally irradiated granulocyte-macrophage colony-stimulating factor (GM-CSF) gene-transfected autologous melanoma and sarcoma cells. Secondary objectives included validation of the gene delivery technology (particle-mediated gene transfer), determining the host immune response to the tumor after vaccination, and monitoring patients for evidence of antitumor response. Sixteen patients were treated with either of two different doses of GM-CSF-treated tumor cells. One patient received treatment with both doses of tumor cells. No treatment-related local or systemic toxicity was noted in any patient. Patients administered 100% treated cells (i.e., with a preparation of tumor cells that had all been exposed to GM-CSF DNA transfection) had a more extensive lymphocytic infiltrate at the vaccine site than did patients given 10% treated cells (a preparation of tumor cells in which 10% had been exposed to GM-CSF transfection) or nontreated tumor. The generation of a systemic immune response to autologous tumor by a delayed-type hypersensitivity response to the intradermal placement of nontransfected tumor cells was noted in one patient. One patient had a transient partial response of metastatic tumor sites. The entire procedure, from tumor removal to vaccine placement, was accomplished in less than 6 hr in all patients. Four of 17 patient tumor preparations produced greater than 3.0 ng of GM-CSF per 10(6) cells per 24 hr in vitro. The one patient with greater than 30 ng of GM-CSF per 10(6) cells per 24 hr in vitro had positive DTH, a significant histologic inflammatory response, and clinically stable disease. This technique of gene transfer was safe and feasible, but resulted in clinically relevant levels of gene expression in only a minority of patients.

Biolistics↗

Immunohistochemical study of microphthalmia transcription factor and tyrosinase in angiomyolipoma of the kidney, renal cell carcinoma, and renal and retroperitoneal sarcomas: comparative evaluation with traditional diagnostic markers.

Angiomyolipoma has a unique immunophenotype with co-expression of muscle-specific actin and melanocytic markers such as HMB-45 and Melan-A. The most recently developed melanocytic markers, microphthalmia transcription factor and tyrosinase, have not been studied in the diagnosis of angiomyolipoma. We tested 29 renal angiomyolipomas (21 classic histology, 4 epithelioid variants, 2 lipomatous variants, and 2 leiomyomatous variants) with an immunohistochemical panel, including microphthalmia transcription factor, tyrosinase, HMB-45, Melan-A, and muscle-specific actin. Results were compared with 15 renal cell carcinomas (9 conventional types, 6 with sarcomatoid change), 2 leiomyosarcomas, 5 liposarcomas, and 1 unclassified high-grade sarcoma. Microphthalmia transcription factor expression was seen in 22 of 29 angiomyolipomas, one renal cell carcinoma, and one well-differentiated liposarcoma (that is, 2 of 23 non-angiomyolipomas; sensitivity 75%, specificity 91%). Tyrosinase expression was seen in 4 of 29 angiomyolipomas and 0 of 23 non-angiomyolipomas (sensitivity 14%, specificity 100%). HMB-45 was positive in 24 of 29 angiomyolipomas and 0 of 23 non-angiomyolipomas (sensitivity 83%, specificity 100%). Melan-A was expressed by 25 of 29 angiomyolipomas and 0 of 23 non-angiomyolipomas (sensitivity 86%, specificity 100%). Muscle-specific actin was expressed by 29 of 29 angiomyolipomas and 2 of 23 non-angiomyolipomas (both leiomyosarcomas; sensitivity 100%, specificity 91% [100% excluding leiomyosarcomas]). Microphthalmia transcription factor showed the most widespread staining in angiomyolipoma (50% of cases staining more than half of the tumor cells) followed by Melan-A (24% of cases staining more than 50%). Only three cases showed positivity for all four melanocytic markers, while in one case each only microphthalmia transcription factor and Melan-A were positive. We conclude that microphthalmia transcription factor, but not tyrosinase immunostaining, has a sensitivity and specificity that rivals those of the established markers, HMB-45 and Melan-A, in the diagnosis of angiomyolipoma. Our data supports the use of a panel in difficult cases that includes antibodies to microphthalmia transcription factor, either Melan-A or HMB-45, and muscle-specific actin to provide the best mix of high sensitivity, high specificity, nuclear and cytoplasmic immunolocalization, and widespread staining of cells within a given tumor.

Actins↗

Primary retroperitoneal soft-tissue sarcomas.

Of the 98 soft-tissue sarcomas treated between 1973-1978, 12 were retroperitoneal in origin. Fifty percent underwent one to three previous surgical procedures. All patients were operated on. In 75% (nine out of 12), the tumor was completely resected. The operative mortality for total tumor excision was 11%. There were five liposarcomas, three leiomyosarcomas, two neurofibrosarcomas, and one synovial sarcoma and one unclassified sarcoma. Six of the 12 patients survived five years and three (25%) were alive without evidence of disease at 5 years. Three of the completely resected group received no further treatment; 2/3 survived 5 years; three had postoperative chemotherapy; 3/3 survived; and three others had radiation and chemotherapy subsequent to surgery; all three have died. The two most important prognostic factors were tumor grade and surgical excision. Only one patient with high grade tumor survived. Total surgical excision of the tumor offers the only hope for cure. Aggressive surgery in treating retroperitoneal soft part sarcomas is strongly recommended.

Adult↗

Radiation-induced sarcoma of the thyroid.

A 23-year-old white man presented with a thyroid mass 12 years after receiving high-dose radiotherapy for a T2 and N1 lymphoepithelioma of the nasopharynx. Following subtotal thyroidectomy, a histopathologic examination revealed liposarcoma of the thyroid gland. The relationship between sarcomas and irradiation is described and Cahan and colleagues' criteria for radiation-induced sarcomas are reviewed. To our knowledge, we are presenting the first such case of a radiation-induced sarcoma of the thyroid gland.

Adult↗

Distribution pattern of tenascin-C in normal and neoplastic mesenchymal tissues.

Descriptions for tenascin-C distribution are largely restricted to epithelial tumours. The present study utilized newly developed and characterized monoclonal (hT191) and polyclonal antibodies to investigate the distribution pattern of tenascin-C in a panel of mesenchymal tumours, which was contrasted with normal tissue. The specific antibodies recognized the distinctive star-like hexabrachion protein isolated from transformed cell-culture medium and serum from normal individuals. In normal tissues, a strong tenascin-C expression in the extracellular matrix was largely restricted to basement-membrane regions of epithelium and tonsilar sinusoids, pericellularly within smooth-muscle bundles, associated with perimysial, -chondrial, -neurial and -tendon surfaces, and diffusely within vascular adventitia. It was found in the corresponding tumours of the neural sheath (schwannoma) and smooth muscle (leiomyosarcoma), and was abundantly present around certain blood vessels of mesenchymal tumours. Although not detected in normal muscle, or in adipose or fibrous connective tissue, neo-expression of tenascin-C was shown in more than half of the rhabdomyosarcomas, fibromas and liposarcomas, with an increased positive percentage in variably malignant myxoid liposarcomas compared with lipoma-like sarcomas. Tenascin-C was typically found in the extracellular matrix of soft-tissue tumours, but was notably absent from the epithelial-cell components of mixed epithelial/mesenchymal tumours. Its apparently enhanced expression in soft-tissue tumours differs from that of most other large extracellular-matrix proteins, suggesting possible functional involvement of the cell-adhesion molecule, tenascin-C, in the neoplastic phenotype.

Antibodies↗

Light and electron microscopic examination of embedded fine-needle aspiration biopsy specimens in the preoperative diagnosis of soft tissue and bone tumors.

A technique is described for the light- and electron microscopic examination of fine-needle aspiration biopsy specimens in the preoperative diagnosis of soft tissue tumors and bone tumors. The results obtained after studies on 18 soft tissue tumors, five bone tumors, and three metastatic carcinomas, thought to be primary soft tissue tumors, indicate important advantages to be obtained by using this method compared to conventional aspiration cytology: (1) it gives a very well preserved cellular morphology as seen both light and electron microscopically; (2) the preserved tissue structure and growth pattern is of importance for the diagnosis in many soft tissue and bone tumors; (3) some conventional histologic stainings can be applied giving additional information and an appearance familiar to the surgical pathologist; (4) the specimens can be saved in blocks and new sections made whenever necessary; and (5) the opportunity of studying the material under the electron microscope often helps to confirm a suggested diagnosis and may be necessary in some cases in order to arrive at a definite diagnosis.

Biopsy, Needle↗

[Mesenchymal tumors of the pancreas. Surprising, but not uncommon].

Mesenchymal tumors of the pancreas are rare. They are resected because a solid or cystic pancreatic tumor is suspected. Benign mesenchymal tumors comprise lymphangiomas, hemangiomas, schwannomas, solitary fibrous tumors, adenomatoid tumors, clear cell tumors, and hamartomas. Inflammatory pseudotumors are a special case. Malignant mesenchymal tumors include leiomyosarcomas, malignant peripheral nerve sheath tumors (MPNST), liposarcomas, malignant fibrous histiocytomas, Ewing's sarcomas, and primitive neuroectodermal tumors (PNET). It is important to differentiate these tumors from anaplastic carcinomas and retroperitoneal tumors that infiltrate pancreatic tissue.

Adenoma↗

Development of an ELISA for the detection of 2-nitroimidazole hypoxia markers bound to tumor tissue.

Canine and rodent tumors covalently bind the fluorinated 2-nitroimidazole, CCI-103F, in a way that immunohistochemical analysis shows is consistent with the location of tumor hypoxia. We have now developed a rapid, quantitative, and non-radioactive enzyme linked immunosorbent assay for the binding of CCI-103F in biopsy samples of spontaneous canine tumors. Issues of antigen stability during tissue processing, calibration of the ELISA, and the use of biopsy samples for measuring tumor hypoxia by the ELISA approach are addressed.

Animals↗

Chondroid lipoma. A newly described lesion that may be mistaken for malignancy.

A case of chondroid lipoma located in the submandibular region of a 21-year-old man is presented. On macroscopic evaluation the tumor was lobulated and quite yellow. Microscopic examination showed that this tumor was composed of mature adipose tissue and eosinophilic cells. The eosinophilic cells displayed single or multiple vacuoles and resembled lipoblast or hibernoma-like cells. These were set in a myxoid or chondromyxoid stroma. Most cells reacted with antibodies directed against vimentin and neuron-specific enolase. Focal weak positivity for S-100 protein was noted. Principal considerations in the histopathologic differential diagnosis included hibernoma, myxoid liposarcoma, and extraskeletal myxoid chondrosarcoma (chordoid sarcoma).

Adipose Tissue↗

Evaluation of Rare Tumors with [F-18]Fluorodeoxyglucose Positron Emission Tomography.

The purpose of this paper was to evaluate the utility of positron emission tomography (PET) with 2-[18F]fluoro-2-deoxy-D-glucose (FDG) in the clinical assessment of rare tumors. We identified 6 patients over the last 18 months with rare tumors who were referred for PET imaging at the time of initial diagnosis, for tumor surveillance or for posttherapy reevaluation. The PET findings were compared with follow-up clinical data, the results of other imaging modalities and histology. FDG PET correctly detected disease in patients with anaplastic thyroid cancer, pleural mesothelioma, myxoid liposarcoma, malignant fibrous histiocytoma, synovial cell sarcoma and uterine leiomyosarcoma. These findings suggest that PET is useful in the evaluation of a variety of rare tumors both for initial preoperative staging and post-therapy assessment. Further experience with other uncommon tumors is necessary to define the precise role of FDG PET in this clinical setting.

Journal Article↗