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.

Adenosarcoma of the uterine corpus associated with ovarian thecoma.

We describe a case of adenosarcoma of the uterine corpus associated with ovarian thecoma in a 67-year-old woman. The patient underwent surgery under a diagnosis of ovarian carcinoma. The 110 x 70 mm-sized ovarian tumor was diagnosed as thecoma. The polypoid tumor of the uterine corpus which measured 30 x 15 mm was diagnosed as adenosarcoma. Cells of both epithelial and stromal elements of the adenosarcoma expressed estrogen receptors (determined by immunohistochemistry). These findings support the view that estrogen stimulation, including that by a pre-existing ovarian thecoma, may play a role in the development of mesenchymal and mixed epithelial / mesenchymal uterine tumors, including adenosarcoma.

Diverse differentiation in malignant peripheral nerve sheath tumours associated with neurofibromatosis-1: an immunohistochemical and ultrastructural study.

AIMS: The diverse histological features in malignant peripheral nerve sheath tumours (MPNSTs) associated with NF-1 were investigated by immunohistochemical and electron microscopic analysis. Our study is focused on the differentiation of the tumour cells in the heterogeneous components. METHODS AND RESULTS: Twenty-three cases were classified as conventional type, epithelioid type, anaplastic type, and heterogeneous type, and divided into three groups by the presence of S100 protein (S100)-positive cells in each tumour; Group A was defined as having >50% S100+ cells, Group B as having <50%, and Group C as cases with no positive cells. To investigate the differentiation of the tumour cells, the morphology and immunoreactivity for neural or mesenchymal markers among the three groups were compared. For the identification of Schwannian, perineurial, and endoneurial differentiation, markers for S100, EMA and CD34 were used, respectively. In three tumours of the Group A type, there were no cases showing differentiation towards perineurial or endoneurial cells, or formation of heterogeneous components. In nine tumours of the Group B type, one tumour expressed EMA and CD34, suggesting probable perineurial and/or endoneurial differentiation. One tumour showed rhabdomyoblastic differentiation. Three tumours showed cartilaginous or osteogenic differentiation, and one of the three also showed a focal vascular differentiation. The surrounding areas of the heterogeneous components were composed of mixed S100+ cells and S100- cells. S100- cells in the areas were positive for CD34 in one case. In 11 tumours of Group C type, one tumour expressed EMA and CD34 suggesting perineurial and/or endoneurial cell differentiation. Three tumours showed rhabdomyoblastic differentiation. The tumour cells around the heterogeneous components in the three cases were negative for EMA and CD34. CONCLUSION: Our results suggest that tumour cells differentiating to Schwann cells are not the only component of MPNSTs. Furthermore, tumour cells other than Schwann cells are largely related to the formation of the heterogeneous components in MPNSTs associated with NF-1.

Low incidence of genetic alterations of the p16CDKN2a in clear cell chondrosarcoma.

Mutational inactivation of the cyclin-dependent kinase inhibitors (CDKIs) (p16CDKN2a) tumor suppressor gene has been found in a variety of human tumor types. To investigate the involvement of CDKI abnormality in clear cell chondrosarcoma, alterations of CDKIs were examined in clear cell chondrosarcoma tissues using a quantitative DNA/PCR, PCR-SSCP. Two of 38 specimens (5.2%) we analyzed showed abnormally low levels of p16CDKN2a amplification, suggesting that the allelic deletion of the gene might be low frequent event in progression of this tumor. For detection of subtle sequence alterations such as point mutations, we performed SSCP analysis of the entire coding region of the p16CDKN2a gene. No altered SSCP patterns were found in 38 clear cell chondrosarcoma specimens. This study reflects the very low incidence of genetic alterations of the p16CDKN2a gene in clear cell chondrosarcoma. Therefore, we conclude that the alteration of the p16CDKN2a gene is not involved significantly in the development of clear cell chondrosarcoma.

Overexpression of p53 and absent genetic mutation in clear cell chondrosarcoma.

Clear cell chondrosarcoma is one of the extremely rare chondrosarcomas. The pathogenesis and the molecular genetic events, which contribute to the development of clear cell chondrosarcoma, are not well elucidated, due in part to the lack of sufficient tumor tissue available. To characterize the involvement of the p53 gene abnormality in this disease, we analyzed expression and sequence alteration of p53 by immunohistochemical analysis of the protein expression and quantitative DNA/PCR and PCR-SSCP assays of the gene in 28 paraffin-embedded tissue specimens. Immunohistochemical analysis demonstrated that 7 (25%) showed patchy positive nuclear staining for p53 and 5 (18%) showed diffuse positive nuclear staining patterns. Sixteen (57%) were negative for p53 immunostaining. Quantitative DNA/PCR analysis revealed that none of the cases we studied showed significantly reduced levels of p53 amplification (<0.50), strongly suggesting an allelic deletion of the p53 gene. In contrast, however, DNA/PCR-SSCP analysis failed to detect any types of mutations resulting in amino acid substitution within exons 5-9 regions of the gene. Taken together, our data suggest that genetic alteration of p53 is a relatively rare event in clear cell chondrosarcomas but a substantial fraction of this type of tumors carries abnormal overexpression of p53, which might result from an as yet unidentified mechanism(s).

[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.

Carcinosarcoma of the liver.

An autopsy case of carcinosarcoma of the liver in an 84-year-old man is described. The 14 x 6-cm solid tumor was located in the hilus to the left lobe and was grayish-white with some translucent areas. Histologically, the tumor consisted of an intimate mixture of adenocarcinomatous and chondrosarcomatous elements with transitional areas in between. Immunohistochemically, cells of the adenocarcinomatous elements were positive for cytokeratin but negative for S100 protein, whereas cells of the chondrosarcomatous elements showed the reverse staining pattern. Cells of transitional areas were positive for both cytokeratin and S100 protein. Most previously reported cases of carcinosarcoma of the liver have involved elderly men and have had a poor prognosis. The findings of the present case support the view that carcinosarcomas represent carcinomas that develop a sarcomatous element via metaplasia of the epithelial element.

p53 gene mutations occurring in spontaneous benign and malignant mammary tumors of the dog.

Sixty-three cases of benign and malignant canine mammary tumors were analyzed to define the alteration of exons 5-8 for the p53 tumor suppressor gene using polymerase chain reaction direct sequence analysis with paraffin-embedded tissues. Four missense mutations were found in 38 benign mammary tumors (11%), and five missense (one tumor had two missense mutations) and one nonsense mutations were found in 25 mammary carcinomas (20%). These data suggest that the p53 gene alterations might be initiated at an early stage of canine mammary carcinogenesis and p53 mutations might be associated with malignancy. However, there was no evidence of any relationship between the p53 alterations and the histologic types of tumors or breeds of dogs.

An extremely large solitary primary paraganglioma of the lung: report of a case.

We present herein the case of a 38-year-old woman found to have an extremely large solitary primary paraganglioma of the lung. The patient presented with chest pain on exertion and a mass was discovered in the left lower lobe of the lung by chest X-rays and computed tomography (CT). As no other neoplasms were detected elsewhere, a left lower lobectomy was performed. The patient has remained well without any evidence of recurrence for 5 years since her operation. The tumor, measuring 13 x 12 x 7 cm, was composed of ovoid cells (Zellballen), which were positive for Fontana-Masson and Grimelius stains, and sustentacular cells. Immunohistochemically, the ovoid cells were positive for neuron-specific enolase, S-100, CAM5.2, Leu7, and chromogranin A, and negative for carcinoembryonic antigen and epithelial membrane antigen. The sustentacular cells were positive for S-100 protein and CAM5.2, and negative for glial fibrillary acid protein. Therefore, the tumor was diagnosed as a paraganglioma. The tumor from our patient is the largest of the 17 solitary primary pulmonary paragangliomas reported thus far in the English-language literature.

Radiation-induced inflammatory malignant fibrous histiocytoma of the ileum.

A case of inflammatory malignant fibrous histiocytoma of the ileum seemingly induced by radiation is described. A 50-year-old female with a past history of uterine cervical carcinoma and postoperative radiation therapy presented with abdominal pain, fever and leukocytosis. The subserosa of the distal part of the ileum showed a diffuse dense, neutrophilic and lymphocytic infiltrate with dispersed atypical, short spindle- or plump oval-shaped histiocyte-like cells. Pleomorphic mono- or multinucleated giant cells with bizarre nuclei were also intermingled in the lesion. Immunohistochemically, the tumorous atypical cells were positive for vimentin, alpha-smooth muscle actin, alpha-1 antitrypsin and granulocyte colony-stimulating factor. No EBV genomic sequences were detected by in situ hybridization. Flow cytometry showed an aneuploid DNA content with high S-phase fraction. The patient was well with no evidence of tumor at 5 months after surgery. It is important to include this type of tumor in the differential diagnosis of small intestinal lesions accompanied by fever and leukocytosis following radiation.

Collagenous fibroma (desmoplastic fibroblastoma): a distinctive fibroblastic soft tissue tumor.

Collagenous fibroma is a distinct, benign, fibroblastic/myofibroblastic proliferation, probably neoplasm. It is a slow-growing tumor arising in predominantly subcutaneous tissue. This tumor is composed of stellate-shaped fibroblasts and abundant interstitial collagen. Since none of reported collagenous fibromas recurred, simple excision is an appropriate treatment. Collagenous fibroma should be differentiated from fibromatosis, which has a high risk of local recurrence if simple local excision is done. Fibromatosis is more cellular and shows short fascicular arrangements of tumor cells and greater infiltration at the periphery than collagenous fibroma.

Osteosarcoma of the metatarsal bone.

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

Proximal-type epithelioid sarcoma in the pelvic soft tissues.

A case of proximal-type epithelioid sarcoma arising in the pelvic soft tissues of a 46-year-old man is presented. The tumor showed a predominantly epithelioid component with rhabdoid features, cord-like arrangement, small nests, abundant eosinophilic cytoplasm containing intracytoplasmic, paranuclear, hyaline-like globules, large vesicular nuclei, and prominent nucleoli. There were foci with alveolar arrangement and a spindle-cell proliferation. The tumor cells were positive for cytokeratin CAM5.2, vimentin, epithelial membrane antigen, and CD34. Flow cytometry showed a diploid DNA content with high S-phase fraction. The patient had pelvic lymph-node metastases. He died of the disease 5 months after diagnosis. It is important to include proximal-type epithelioid sarcoma in the differential diagnosis of pelvic tumors.

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.

Expression of vascular endothelial growth factor in N-butyl-N-(4-hydroxybutyl)nitrosamine-induced rat bladder carcinogenesis.

Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) are proteins implicated in tumor-associated microvascular angiogenesis. Expressions of VEGF and bFGF in various stages of chemical-induced rat bladder carcinogenesis were immunohistochemically investigated. Thirty-two male 6-week-old Wistar rats were given drinking water containing 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) for 20 weeks. VEGF and bFGF were not detected in the normal bladder epithelium. In simple hyperplasia, intensive expression of VEGF was observed in a few epithelial cells, and the expression of epithelial VEGF became more pronounced in papillary or nodular (PN) hyperplasia and papilloma. In carcinoma, heterogeneous expression of VEGF was observed in focal tumor cells, intensely expressed in the invading tumor cells. Ultrastructurally, carcinoma cells showed VEGF immunoreactivity in the cytoplasmic matrix and some rough endoplasmic reticulum, and VEGF-positive and -negative carcinoma cells were also clearly defined. High levels of VEGF mRNA were observed in the carcinoma. However, bFGF was not detected in the epithelium throughout the carcinogenesis. Increased microvessel counts appeared at simple hyperplasia and became more pronounced in PN hyperplasia, papilloma, and carcinoma (F-test; P < 0.05). In the carcinoma, the microvessel counts of the VEGF-expressing tumor areas were significantly higher than that of the non-VEGF-expressing tumor areas (U-test; P < 0.05). The present study suggests that upregulation of epithelial VEGF may begin at a quite early stage in BBN-induced rat bladder carcinogenesis, but bFGF may not be involved.

Periosteal Ewing-like adamantinoma.

We report a Ewing-like adamantinoma of the periosteal region of the right tibia in a 15-year-old boy. The tumour was well demarcated but unencapsulated and showed cortical bone erosion. Histologically, the neoplastic cells were arranged in trabecular and cord-like patterns with fibrous, hyalinized, and myxoid stroma. Cellular atypia was mild, and mitotic figures were rarely seen. Many tumour cells expressed wide keratin, epithelial membrane antigen, leu 7, synaptophysin, Ewing's sarcoma-related antigen O13, and some were positive for neuron-specific antigen, vimentin, and CD68. The tumour was negative for S-100 protein, desmin, alpha-smooth muscle actin, and muscle-specific actin. Flow cytometric analysis showed that the tumour was aneuploid. After wide excision the patient has been well for the 16 months since diagnosis.

Papillary adenocarcinoma arising in placentoid bullous lesion of the lung: report of a case with immunohistochemical study.

We report the case of a 52-year-old man with papillary adenocarcinoma arising in placentoid bullous lesion of the lung, which is a rare cystic lung disease. Macroscopically, the cyst contained a soft villous tumor closely resembling the placental chorionic villi of early gestation. Histologic examination revealed the tumor to be papillary adenocarcinoma with an abundant stromal core, which comprised vascular and lymphatic vessels, lymphocytes, fat cells, and smooth muscle. Immunohistochemically, adenocarcinoma cells were positive for CAM 5.2, epithelial membrane antigen, and PE10 (antisurfactant apoprotein A antibody). These results indicate that the adenocarcinoma was derived from the component epithelial cells of the cyst. Based on the tumor's macroscopic and microscopic appearance and on the results of the immunohistochemical studies, we conclude that the cystic tumor in our case arose in a placentoid bullous lesion of the lung.

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.

Small cell (oat cell) carcinoma of the breast.

A case of small cell (oat cell) carcinoma, which represents both the most distinctive and the least common type of breast carcinoma with neuroendocrine differentiation and usually shows the most aggressive behavior, is described. Radical mastectomy was performed on a 56-year-old female for a 10 cm tumor located in the outer part of the right breast with cutaneous ulceration Microscopically, the tumor predominantly consisted of a diffuse proliferation of small, round to ovoid cells with hyperchromatic nuclei and ill-defined, scant cytoplasm that was reminiscent of oat cell carcinoma of the lung. There were foci of invasive ductal carcinoma and ductal carcinoma in situ. Small cell carcinoma areas constituted approximately 90% of the neoplasm. The patient had axillary lymph node metastasis. The small tumor cells were argyrophilic and positive for CAM5.2, carcinoembryonic antigen, neuron-specific enolase, Leu-7, chromogranin A and synaptophysin. Flow cytometric analysis showed an aneuploid DNA content. The patient was alive and well without disease 4 years after surgery. Small cell carcinomas of the breast may exhibit a spectrum of malignancy that is comparable to similar tumors at better known primary sites.