A malignant peripheral nerve-sheath tumour responding to chemotherapy.

A malignant peripheral nerve-sheath tumour developed in the right S1 nerve root in a man aged 30 causing back pain and sciatica. CT and MRI revealed a destructive tumour of the sacrum invading the retroperitoneal space. The tumour was not resectable with an adequate margin. Chemotherapy, consisting of high-dose ifosfamide followed by a combination of vincristine, doxorubicin and cyclophosphamide, was given with success. Malignant peripheral nerve-sheath tumours are thought to respond weakly to chemotherapy, but the response in our patient was complete.

Chondroblastoma: a study of 11 cases.

AIM: Chondroblastoma is an infrequent and unique neoplasm that is histologically characterized by chondroblastoma cells, osteoclast-like giant cells and sometimes reactive osteoid. Although it is generally regarded as benign, it may recur and sporadically metastasize to the lung. Many important questions concerning the prognostic factors and adequate surgical treatment of chondroblastoma have not been fully answered and remain controversial. The purpose of this study was to determine clinicopathological features useful in prediction of the tumour behaviours. METHODS: Eleven chondroblastoma cases were reviwed clinicopathologically. According to Enneking's radiographic grading system, seven cases were classified as stage I, three cases as stage II and one case was classified as stage III. RESULTS: Nine cases had initially been treated with simple curettage, one had aggressive curettage applied as a primary surgery and one underwent amputation. Among the nine simple curettage cases, one recurred and was reoperated with aggressive curettage. Adjuvant treatment (alcohol and/or cement) was applied in the two aggressive curettage cases; none demonstrated further tumour recurrence. All lesions were curettaged, and one case recurred. The rate of proliferating-cell nuclear antigen expression was significantly higher in the recurrent case. CONCLUSION: The recurrent case seemed to have a high growth activity. Simple curettage was effective for local control during the initial treatment in most cases, but aggressive curettage and adjuvant treatment with alcohol and/or cement was useful for local control in recurrent chondroblastoma and chondroblastoma presenting with an aggressive behaviour.

Prevention of neonatal estrogen imprinting by vitamin A as indicated by estrogen receptor expression in the mouse vagina.

Treatment of female mice with estrogen during the neonatal period induces estrogen-independent persistent proliferation and cornification of the vaginal epithelium when the animals become adults. However, the occurrence of such irreversible vaginal changes is blocked by concurrent retinol acetate (RA) treatment. This study aimed to determine the expression pattern of estrogen receptor (ER) alpha and beta in the vaginas of ovariectomized 35-day-old mice treated neonatally with 17beta-estradiol (E(2)) and/or RA. The amounts of ERalpha and ERbeta mRNA molecules in the vaginal RNA samples were determined by competitive reverse transcription/polymerase chain reaction. The levels of both mRNAs were lower in ovariectomized mice that had been treated neonatally with E(2) but not in those treated with E(2) plus RA. Neonatal E(2) treatment caused a decrease in the percentage of ERalpha-immunoreactive cells in the vaginal stroma during adulthood, and concurrent RA treatment inhibited the decrease. The amount of each ER mRNA was also measured in the vaginas of mature mice treated with E(2) and RA; no inhibitory activity of RA was seen in the mature mice. Our studies indicate that, in mouse vagina, the irreversible effects of neonatal imprinting by estrogen might be prevented by the simultaneous administration of vitamin A through the inhibition of a decrease of the number of ER-expressing cells.

Suppression of the development of experimentally induced uterine adenomyosis by a novel matrix metalloproteinase inhibitor, ONO-4817, in mice.

The inhibitory effects of a novel, orally active matrix metalloproteinase (MMP) inhibitor, ONO-4817, on the development of uterine adenomyosis induced experimentally by pituitary grafting were examined in mice. Mice were given transplants of isologous anterior pituitary glands (PGs) into the right uterine lumen at 7 weeks of age and were fed chow containing 0.1% to 1.0% ONO-4817 from 8 to 14 weeks of age. Mice treated with 0.3% or 1.0% ONO-4817 showed a significantly lower incidence of the development of adenomyosis than vehicle-treated mice. To evaluate the inhibitory effects of ONO-4817 on the progression of the invasion of the adenomyotic tissues, mice receiving PG grafts at 7 weeks of age were treated with 1.0% ONO-4817 from 13 to 17 weeks of age. The degree of pathological progression of adenomyosis was graded from 1 to 5 in increments of 1. The degree of the progression of the lesion was less in the uteri exposed to ONO-4817 (2.71 +/- 0.93) than in the uteri not exposed to the inhibitor (4.33 +/- 0.75). Finally, the invasiveness of endometrial stromal cells obtained from adenomyotic uteri into Matrigel consisting mainly of type IV collagen and laminin was examined using an invasion assay. The assay showed that the treatment with ONO-4817 markedly suppressed the invasion of the stromal cells of the adenomyotic uteri into the gel. These results indicate that ONO-4817 may be an effective inhibitor of the development of adenomyosis.

[Usefulness of immunohistochemistry as a diagnostic tool for tumors and pseudotumoral bone lesions]. / Utilité de l'immunohistochimie comme aide au diagnostic des tumeurs et des lésions pseudotumorales osseuses.

Immunohistochemical study for the diagnosis of bone tumors and tumor-like lesions has to be scheduled after an appropriate analysis of clinical data, radiological findings, and results of histology in H-E sections. The value of several markers for osteoblasts is discussed, chiefly for various forms of osteosarcomas. In the same way, the role of S-100 protein as well as anticollagen type II antibody is developed for cartilaginous tumors. The selection of markers in the fields of round cell tumors and spindle cell tumors of bone is also discussed. Some diagnostic problems with the support of immunohistochemistry are described, like chordomas versus chondrosarcomas or bone metastases. Lastly, immunohistochemical study of proliferating factors in the bone tumor field is quoted.

Synovial sarcoma, histologically mimicking primitive neuroectodermal tumor/Ewing's sarcoma at distant sites.

We report a case of synovial sarcoma (SS) showing unusual histology at distant sites. A 47-year-old man was aware of a tumor on the sole of his left foot. After preoperative chemotherapy with a diagnosis of SS, wide excision was performed. During postoperative chemotherapy, multiple tumorous lesions developed in the bone (including the whole spine) and both lungs. The patient died 1 year later. Histologically, the excised tumor of the foot showed a biphasic cellular pattern typical of SS, whereas at autopsy the bone and lung lesions were composed only of undifferentiated small round cells with cytoplasmic fibrillar processes. Homer-Wright rosettes were also observed. Immunohistochemically, 80% of the bone and lung tumor cells expressed MIC2 protein homogeneously. To clarify whether the bone and lung round cell tumors were metastatic lesions or second malignancies, especially primary primitive neuroectodermal tumor (PNET)/Ewing's sarcoma (ES), we performed reverse transcription-polymerase chain reaction (RT-PCR) analysis of tumor type-specific fusion gene transcripts. The SYT/SSX fusion transcript was identified in both the foot and lung lesions, whereas the EWS/FLI1 transcript was not detected in either lesion. Therefore, we concluded that the multiple bone and lung tumors were poorly differentiated metastatic tumors, which arose from the SS of the foot. We also conclude that the identification of chimeric fusion transcripts can be successfully applied to poorly differentiated sarcomas and will help in the differential diagnosis of tumors that cannot be distinguished by conventional morphological examinations. Also, it should be remembered that cytoplasmic staining for MIC2 protein may occur in sarcomas other than PNET/ES.

Osteosarcoma of the metatarsal bone.

A case of osteosarcoma arising from a metatarsal bone is reported, focusing on the radiological findings and differential diagnosis.

Evaluation of new monoclonal anti-MyoD1 and anti-myogenin antibodies for the diagnosis of rhabdomyosarcoma.

New monoclonal anti-MyoD1 and anti-myogenin antibodies were evaluated immunohistochemically to determine whether they are useful in discriminating rhabdomyosarcoma (RMS) from other soft tissue tumors in routinely processed sections. Neither MyoD1 nor myogenin was expressed in normal, mature striated muscle. In RMS, nuclear expression of MyoD1 and myogenin was found in 82 and 80% of non-overlapping cases, respectively. MyoD1 was generally expressed in small, primitive tumor cells, and larger cells exhibiting morphological evidence of skeletal muscle differentiation failed to express positive nuclear immunostaining. Positive nuclear staining for myogenin was stronger than that for MyoD1 in cases with abundant differentiated tumor cells, but was less prominent in cases in which small, primitive tumor cells predominated. No leiomyosarcomas, Ewing's sarcomas/peripheral primitive neuroectodermal tumors or other soft tissue tumors exhibited nuclear expression of MyoD1 or myogenin. In conclusion, both anti-MyoD1 and anti-myogenin antibodies are useful for diagnosing RMS and for discriminating RMS from other soft tissue tumors.

Clear cell chondrosarcoma: a pathological and immunohistochemical study.

AIM: Clear cell chondrosarcoma (CCC) is a rare malignant cartilaginous neoplasm of bone. CCC is characterized by clear cells (CCC cells), osteoclasts and osteoblasts. Many important questions concerning the varied histological features of CCC, and the interactions between CCC cells and coexisting osteoclasts and osteoblasts have not been fully investigated and remain controversial. The aim of this study is to clarify and explain the varied histological features and the possible interaction between tumour cells (CCC cells) and stromal cells such as osteoclasts and osteoblasts. METHODS AND RESULTS: Four cases of CCC were histologically and immunohistochemically studied in order to elucidate the biological nature and histological characteristics. A comparative study with chondroblastoma and grade I conventional chondrosarcoma (CC) was also performed. S100 protein and type II collagen were expressed in CCC cells, chondroblastoma cells and CC cells. CD68 and matrix metalloproteinase-9 were expressed in coexisting histiocytes and osteoclasts. Parathyroid hormone-like protein (PTH-LP) was expressed in histiocytes, osteoclasts, osteoblasts, chondroblastoma cells and CCC cells. Platelet-derived growth factor (PDGF) and its receptor (PDGF-R) were observed in osteoblasts, chondroblastoma cells and CCC cells. However, PTH-LP, PDGF and PDGF-R were not expressed in CC cells. PCNA (proliferating-cell nuclear antigen) was expressed more intensely in CCC than in chondroblastoma. CONCLUSION: These observations suggest that CCC cells trigger the varied histological changes in association with several cytokines. The difference of PCNA expression between CCC and chondroblastoma seemed to be related to the biological difference between the two tumours.

Giant cell tumor of bone: a clinicopathologic study of prognostic factors.

Forty-seven cases of giant cell tumor of bone were clinicopathologically reviewed to determine any useful prognostic factors. Disease recurred in 11 cases. Eight of these cases had initially been treated with intracapsular piecemeal excision and three cases had been treated with wide excision. Nine of the 11 cases were classified as Grade III, two cases as Grade II, and one case as Grade II + fracture according to Campanacci's radiographic grading system. Intracapsularly excised cases had a high recurrence rate (47.1%). Metastasis to the lung occurred in three cases, each of which had been classified as Grade III. Although the radiographic Grade did not correlate with the rate of lung metastasis or recurrence, cases that metastasized to the lung or recurred tended to be radiographically aggressive. Disease recurred in eight of 24 Grade III cases; but in only two of 12 Grade II cases, in one of five Grade II + fracture cases, and none of six Grade I cases. p53 was expressed by mononuclear stromal cells in six cases. Disease recurred in four and lung metastasis occurred in three of these cases. p53 Expression correlated with rates of lung metastasis and recurrence. It was concluded that cases in which p53 is expressed have a high potential for lung metastasis and recurrence.

Ganglion cells in Ewing's sarcoma following chemotherapy: a case report.

A case of Ewing's sarcoma of the bone, arising in the right radius of a 12-year-old girl, which showed unique histologic features after pre-operative treatment, is reported. The light microscopic features of a biopsy sample were those of a small round cell tumor showing positive immunoreaction with antibodies against the product of the MIC 2 gene (O13), neuron-specific enolase, neurofilament, and synaptophysin, but no morphological differentiation. The patient received combined intensive multi-drug chemotherapy and radiation before surgery. Examination of the surgical specimen showed that the tumor was less cellular than that in the biopsy specimen, and was composed mainly of loosely textured large cells mimicking ganglion cells, occasionally forming Homer-Wright rosettes. An immunohistochemical study revealed that neural differentiation was enhanced. Immunoreactivity for Leu-7 also became positive. Although the patient underwent postoperative chemotherapy, she died of multiple lung and bone metastases 30 months after the diagnosis. Autopsy showed that metastatic foci were made up of densely packed small round cells like those seen in the biopsy samples, but associated with prominent Homer-Wright rosettes. To the authors' knowledge, this is the first report of a tumor being replaced almost entirely by ganglion cells after pre-operative chemotherapy and radiotherapy.

Giant cell tumor of bone: an immunohistochemical comparative study.

Forty-seven cases of giant cell tumor (GCT) of bone were reviewed pathologically to elucidate the origin of spindle-shaped stromal cells or the histogenesis of mononuclear histiocytic stromal cells and osteoclast-like giant cells (OCGC). To clarify the histogenesis of OCGC, eight cases of sarcoma associated with OCGC were reviewed for a comparative study. Spindle-shaped stromal cells sometimes produced minute focl of osteoid matrix. Proliferating cell nuclear antigen (PCNA) was observed in spindle-shaped stromal cells and mononuclear histiocytic stromal cells, but not in OCGC. Matrix metalloproteinase (MMP)-9 was expressed by mononuclear histiocytic stromal cells and OCGC, and its expression was correlated with the lung metastasis rate. In both GCT and sarcomas with OCGC, mononuclear histiocytic stromal cells and OCGC expressed CD68, parathyroid hormone-like protein (PTH-LP), MMP-1 and MMP-9. Immunoreactivity of mononuclear histiocytic stromal cells and OCGC to CD68, PTH-LP, MMP-1 and MMP-9 was similar between GCT and sarcomas with OCGC. These observations may suggest that mononuclear histiocytic stromal cells and OCGC are reactively induced with several cytokines acting in an autocrine or paracrine fashion and that these cells are closely related with the biologic aggressiveness of GCT.

Retiform haemangioendothelioma.

A case of retiform haemangioendothelioma (RH), a recently described rare cutaneous low-grade angiosarcoma, is presented. A 75-year-old female had a 3.5 cm cutaneous nodule in her right lower thigh with 10 year preoperative duration. Microscopically, the dermis and subcutis contained a diffuse and infiltrative neoplasm which was characterized by long arborizing blood vessels arranged in a retiform pattern lined by cuboidal and flattened cells, occasional hobnail appearance of endothelial cells, and a prominent small lymphocytic infiltrate. Small solid areas were also found. Neither significant cellular atypia nor mitotic activity was observed. Immunohistochemically, the tumour cells reacted with endothelial markers (CD31, CD34, factor-VIII-related antigen) and bound Ulex europaeus agglutinin 1. There was no pericytic component within the tumour. The tumour was diploid by flow cytometry. The patient had a local recurrence 27 months after the excision. These findings support the view that RH is a low-grade angiosarcoma and indicate that RH must be distinguished from conventional angiosarcoma.