Malignant fibrous histiocytoma of the gallbladder

We report two extremely rare cases of primary malignant fibrous histiocytoma (MFH) of the gallbladder. The first case occurred in a 70 year old woman who presented with a large tumor of the gallbladder and multiple liver metastases. The second case involved a 74 year old man with a small submucosal tumor of the gallbladder and a single large liver metastasis. Histologically, these tumors consisted of spindle cells in a storiform pattern intermingled with bizarre giant cells. Both of these patients died of liver failure 3 months post-operatively.     

Enhanced expression of catalytic subunit isoform PP1 gamma 1 of protein phosphatase type 1 in malignant fibrous histiocytoma

The expression of the three catalytic subunits of protein phosphatase (PP) type 1 and 2A, PP1 alpha, PP1 gamma 1, and PP2AC, was examined in malignant fibrous histiocytoma using immunohistochemical analysis. The percentage of cells stained positively with antiserum against PP1 catalytic subunit isoform PP1 gamma 1 was significantly higher in tumorous region than in non-tumorous region of malignant fibrous histiocytoma. Furthermore, tumorous region showed markedly high S-phase fraction in the cell cycle, as compared to non-tumorous region. These results suggest that PP1 gamma 1 is involved in the accelerated growth of tumor cells in malignant fibrous histiocytoma.     

DNA aberrations in the epithelial cell component of adamantinoma of long bones

Adamantinoma of long bones is a rare malignant tumor composed of cells with epithelial characteristics in various differentiation patterns surrounded by fibrous cells. Evidence as to whether this neoplasm should be designated as an epithelial bone tumor or a biphasic sarcoma with both epithelial and mesenchymal features is lacking. In this study the nature of the mesenchymal and epithelial components of adamantinoma was investigated by DNA flow cytometry, DNA image cytometry, p53 immunohistochemistry, and polymerase chain reaction-based loss of heterozygosity detection at the p53 locus. Specimens from 6 of 15 patients (40%) analyzed by flow cytometry had an aneuploid DNA index. Image cytometry analysis of Feulgen-stained paraffin sections of 6 aneuploid and 2 diploid tumors revealed that aneuploid nuclei were detected in cells with an epithelial phenotype only, whereas all fibrous cells were diploid. Immunohistochemistry for p53 on specimens from 25 patients revealed moderate or strong immunoreactivity in 12 tumors (48%) restricted to the epithelial cells. Loss of heterozygosity at the p53 locus could be confirmed in the epithelial component of an immunohistochemically p53-positive tumor. Additionally, sections of 7 lung metastases were studied histologically. Only keratin-positive epithelial cells, predominantly in the spindle cell pattern, were present in these metastases, whereas the osteofibrous tissue present in the primary tumors was not detected. These results suggest that either adamantinoma consists of a malignant epithelial part with a reactive osteofibrous stroma or that the malignant epithelial cells develop next to a proliferating benign fibrous component. Additional analysis of common genetic abnormalities in the fibrous and epithelial cells of adamantinoma is therefore indicated.     

Different left ventricular relaxation parameters in isolated working rat and guinea pig hearts. Influence of preload, afterload, temperature, and isoprenaline

Six primary lung tumors with numerous multinucleated osteoclast-like giant cells (OLGCs) and no osteogenic component were evaluated histologically and immunohistochemically to examine pulmonary lesions inciting an OLGC response. The patients comprised four women and two men ranging in age from 61 to 80 years (average age, 69 years). The tumors consisted of one adenocarcinoma, two sarcomatoid carcinomas, and three giant cell variants of malignant fibrous histiocytoma. One tumor was endobronchial in location, while five were situated peripherally. Tumor diameter spanned from 1 to 6.5 cm (average, 2.7 cm). In addition to the giant cells, common characteristics included the malignant nature of the neoplasms and, in five of six cases, histologically malignant mesenchyme. This array of cases exemplifies the variability of lung lesions which may elicit an OLGC inflammatory response resulting in areas resembling the giant cell variant of malignant fibrous histiocytoma. The results of this study suggest that OLGCs occur preferentially in malignant rather than benign nonosteogenic lung tumors and that sarcomatoid regions of malignant tumors are more likely to be infiltrated by OLGCs than epithelial regions.     

Congenital diaphragmatic hernia: an unsolved problem

Primary and metastatic malignant fibrous histiocytoma of the alimentary tract is uncommon, even though it is the most frequently diagnosed malignant soft tissue tumor in adults. In this report, we describe a case of malignant fibrous histiocytoma of the colon.     

Surgical significance of telomerase activity in noncancerous liver tissue from patients with hepatocellular carcinoma

Telomerase activity has been detected in tissue from noncancerous liver of patients with chronic liver disease, but its functional significance remains to be elucidated. We therefore evaluated the telomerase activity in surgically obtained noncancerous liver tissue from 20 hepatocellular carcinoma (HCC) patients. Two samples of noncancerous liver tissue were obtained from each patient: one from the parenchyma adjacent to the HCC nodules of the resected specimen; the other from the parenchyma distant from the HCC nodules of the remnant liver. Telomerase activity was assayed by a non-radioisotope quantitative system based on "TRAP-eze." Five samples from the noncancerous liver tissue adjacent to the HCC nodules (25.0%) were telomerase-positive; all such cases showed high-grade malignant potential, such as intrahepatic metastasis and/or portal vascular invasion and infiltration of the fibrous capsule in the corresponding HCC nodules, and telomerase positivity showed neither a relationship with the histological activity index scores nor a correlation with liver function. Interestingly, no telomerase activity was detected in any of the 20 samples obtained from the parenchyma of the remnant liver. These results indicate that telomerase in noncancerous liver tissue is associated not with the hepatic condition accompanying HCC, but with the biological characteristics of the tumor itself, and may derive from infiltrating cancer cells. Determination of telomerase status may aid in designing more effective surgical procedures.     

Malignant fibrous histiocytoma metastases to the small intestine and colon presenting as an intussusception

A case of malignant fibrous histiocytoma metastases to the small intestine and colon presenting as an intussusception is described. Although malignant fibrous histiocytoma is the most common soft tissue sarcoma in late adult life, GI involvement has rarely been reported. The review of both our case and eight cases in the English-language literature suggests that GI involvement from malignant fibrous histiocytoma occurs most frequently in the small intestine (six of nine) and that two major clinical manifestations of GI involvement are GI bleeding (five of nine) from ulcerated tumors and intussusception (two of nine) led by polypoid tumors.     

Neutrophil chemotactic factors produced by malignant fibrous histiocytoma cell lines

The clinicopathological features of malignant cells are sometimes modified by autologous cytokine production. Inflammatory fibrous histiocytoma (IFH) is characterised by leukocyte infiltration and is a variant of malignant fibrous histiocytoma (MFH). We demonstrated that three MFH cell lines (MF-1, MF-3, and MF-4) have the potential to promote neutrophil chemotaxis and to express mRNA for the cytokines, granulocyte-macrophage colony stimulating factor (GM-CSF) and/or interleukin 8/neutrophil attractant/activation protein 1 (IL-8/NAP-1), both with and without interleukin 1 beta (IL-1 beta) stimulation. MF-1 cells showed the spontaneous production of neutrophil chemotactic activity and the expression of both of GM-CSF and IL-8/NAP-1 mRNA, which was enhanced by exogenous IL-1 beta. In contrast, MF-3 cells showed the expression of GM-CSF and IL-8/NAP-1 mRNA with IL-1 beta stimulation but not without it, and MF-4 cells expressed only IL-8/NAP-1 mRNA when stimulated with IL-1 beta (time- and dose-dependent expression). These findings suggest that neutrophil chemotactic cytokines derived from IFH cells might be responsible for the prominent infiltration of neutrophils in this disease.     

LN-2 (CD74). A marker to distinguish atypical fibroxanthoma from malignant fibrous histiocytoma

BACKGROUND: In this study, the authors examined the expression of LN-2, an antigen expressed by B cells, macrophages, and Reed-Sternberg cells, in a variety of spindle cell lesions of the skin to determine whether LN-2 immunoreactivity can be used to differentiate among these tumors. For comparison, they examined CD34 antigen expression in these lesions, which has been shown to be a useful marker in differentiating dermatofibrosarcoma protuberans from dermatofibroma. METHODS: Immunocytochemistry with anti-LN-2 and anti-CD34 monoclonal antibodies on formalin fixed, paraffin embedded material was performed on 102 spindle cell lesions, including dermatofibroma, dermatofibrosarcoma protuberans, atypical fibroxanthoma, malignant fibrous histiocytoma, leiomyoma, and neurofibroma. RESULTS: LN-2 immunoreactivity did not distinguish between dermatofibroma and dermatofibrosarcoma protuberans, both of which showed weak immunoreactivity. In marked contrast, 90% of cases of malignant fibrous histiocytoma showed strong staining for LN-2, whereas the vast majority (90%) of cases of atypical fibroxanthoma were negative or stained only weakly with anti-LN-2 antibodies. Of the two cases of atypical fibroxanthoma that stained strongly for LN-2, both lesions were > 2 cm in size and extended deep into the subcutaneous fat. CONCLUSIONS: Differential expression of the LN-2 antigen by atypical fibroxanthoma and malignant fibrous histiocytoma distinguishes these two lesions and suggests that acquisition of LN-2 positivity may be a marker of tumor progression.     

Peroxisome proliferator-activated receptor gamma activators inhibit gene expression and migration in human vascular smooth muscle cells

Mesenchymal hamartomas of the liver are the second most common benign liver tumor of childhood. The experience with this tumor at Egleston's Children Hospital at Emory University from 1989 to 1994 is reviewed. Eight patients presented with abdominal distention or an upper abdominal mass. Six patients presented at a mean age of 8 months, and two patients presented at 17 and 23 years of age, respectively. Four patients displayed normal alpha-fetoprotein levels, whereas one patient had an elevated level. Liver function studies were normal in all patients. Abdominal ultrasonography and CT scans revealed a cystic, septated mass within the liver or on a pedicle in all patients. Five patients had simple excision of the tumor, and two had major hepatic resections. The cysts were multiloculated and lined with cuboidal bile duct epithelium surrounded by stroma containing proliferating bile ducts, blood vessels, and compressed liver tissue with no calcifications. In one patient, some pathologists favored the diagnosis of malignant myxoid fibrous histiocytoma because of similar-appearing stroma. Follow-up (mean, 35 months) revealed one symptomatic recurrence after initial resection was incomplete. There were no other recurrences and no malignant transformations. A septated, noncalcified, cystic hepatic mass in an infant with normal liver function studies and characteristic ultrasound or CT is likely a benign mesenchymal hamartoma that can be cured by total local excision.     

Sequence and phylogenetic analysis of the Borrelia burgdorferi secA gene

Adamantinoma of long bones is a rare bone tumour with (immuno-) histological features of epithelial cells, surrounded by various amounts of osteofibrous tissue. Recent studies have indicated that cells with an epithelial phenotype are most probably the malignant element. There is still debate as to whether the fibrous part should be designed as a benign neoplastic element of a biphasic tumour or as a reactive non-neoplastic tissue next to an epithelioid bone tumour. The expression of fibroblast growth factor type 2 (FGF-2), epidermal growth factor (EGF), and their respective receptors FGFR-1 and EGFR, as well as the proliferation marker Ki-67, was studied in both constituents of adamantinoma in serial sections of 25 cases by immunohistochemistry. Expression of FGF-2 and its receptor was present in both constituents of adamantinoma, but predominated in the epithelial component. Expression of EGF and its receptor was restricted to the epithelial component of adamantinoma. Comparing osteofibrous dysplasia (OFD)-like adamantinoma with classic epithelial cell-rich adamantinoma, the expression of FGF-2, EGF, and EGFR was more intense and in a higher percentage of cells in classic adamantinoma. Proliferative activity was found nearly exclusively in the epithelial component. These data further substantiate the hypothesis that epithelial cells constitute the proliferating tumour cell population responsible for the malignant behaviour of adamantinoma. The data indicate that during progression, the epithelial cells acquire expression of FGF-2, EGF, and EGFR, accompanied by a higher proliferative activity. Within the epithelial cell population, there exists an autocrine pathway of growth stimulation. Furthermore, these data point to an interaction between the epithelial and fibrous components, in which the epithelial cells additionally stimulate fibrous cell growth via a paracrine pathway involving FGF-2.     

Giant cell leiomyosarcoma of the spermatic cord: a report

Presentation of the case of one patient with a leiomyosarcoma of the spermatic cord with presence of numerous giant cells, a remarkably unusual finding. Presence of this type of cells, as well as their positivity for histiocytic markers in immunohistochemical staining, raise considerable problems for the differential diagnosis of this neoplasia with malignant fibrous histiocytomas, which probably requires a different, more aggressive therapeutical approach.     

Fibrous dysplasia of the spine, costae and hemipelvis with sarcomatous transformation

We describe a patient with polyostotic fibrous dysplasia and secondary malignant fibrous histiocytoma in a spinal lesion.     

Resection of malignant fibrous histiocytoma invading the thoracic aorta

We report a case of surgically resected malignant fibrous histiocytoma which arose in the posterior mediastinum. Tumor removal with the required sufficient-margin and the resection of the affected thoracic aorta, led to flaccid paraplegia below the tenth thoracic level. This patient is now surviving with no evidence of recurrence at 42 months after the operation. Although malignant fibrous histiocytoma in the thorax generally shows a poor prognosis, this patient with complete resection could have a relatively long survival.     

Single somatic ras gene point mutation in soft tissue malignant fibrous histiocytomas

The frequency of ras gene mutations in human soft tissue malignant fibrous histiocytomas within and around the hot spot codons (12, 13, and 61) of all ras genes, (H-ras-1, K-ras-2, and N-ras) was studied by nested polymerase chain reaction and direct DNA sequencing from archival formalin-fixed, paraffin-embedded tissue. Light microscopy and immunohistochemistry served to define malignant fibrous histiocytoma. All of the four differentiation subtypes (storiform-pleomorphic, inflammatory, myxoid, and giant cell) were investigated. Nine of thirty-two malignant fibrous histiocytomas (28%) contained ras gene point mutations. The highest incidence was found in the myxoid subtype (four of nine). H-ras-1 gene codon 12.2 was the only codon affected and contained in all mutated cases a GGC-->GTC exchange. Seven of the nine mutations were homozygous and probably affected more than 80% of the tumor DNA. The flanking regions of all hotspot codons did not contain any point mutation. The presence of a single and often homozygous point mutation of the H-ras-1 gene, especially in myxoid malignant fibrous histiocytoma could serve as a basis for further genomic discrimination of myxoid sarcomas.     

Expression of the tissue metalloproteinase inhibitors TIMP-1 and TIMP-2 in malignant fibrous histiocytomas and dermatofibromas as studied by in situ hybridization and immunohistochemistry

The expression of tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2) was studied in eight malignant fibrous histiocytomas (MFH) and in eight dermatofibromas (DF) using in situ hybridization methods (ISH). Immunohistochemical stainings were also performed using corresponding antibodies to TIMP-1 and TIMP-2. In ISH the neoplastic cells of MFHs showed a high level of expression for both TIMP-1 and TIMP-2 mRNAs. The cells usually expressed similarly both TIMPs, except for osteoclast-like giant cells, which showed a distinct signal for TIMP-2 but not for TIMP-1. A distinctly lower level of both TIMP-1 and TIMP-2 mRNAs was seen in DFs. Immunohistochemical stainings were concordant with the results obtained by ISH. The findings suggest that the behavior of MFHs and DFs is not directly or solely dependent on the quantity of type IV collagenase inhibitors. The increased TIMP synthesis in MFHs might represent a chaotic response of malignant cells to increased matrix degradation. Alternatively, it may reflect a deranged communication between type IV collagenases and TIMPs in malignant tissues.     

Adrenal pheochromocytoma with both benign and malignant components

A case of adrenal pheochromocytoma is reported characterized by polygonal basophilic granular cells of benign type, plump eosinophilic granular cells of transitional type, and spindle-shaped cells of malignant type. In the primary tumor the neoplastic cells of each type revealed a distinctive topographical distribution. All gradations between the latter two varieties of cells were found, especially in the vicinity of the transitional cell area. Multiple metastases were present in the liver and lungs, where only anaplastic spindle-shaped cells could be found. Ultrastructurally, the benign cells contained predominantly large, rather light, secretory granules with a coarsely granulated core. In the malignant cells, the number, size, and intensity of granules varied considerably from cell to cell or even within a single cell. In general, the malignant cells had a higher frequency of smaller granules with electron-dense homogeneous cores. Moderate amounts of noradrenalin but not significant dopamine or adrenalin could be demonstrated from a metastatic nodule in liver. We postulate that this adrenal medullary pheochromocytoma was benign originally and underwent malignant transformation shortly before the patient's death. This is based upon the patient's clinical features and the peculiar structures of the primary tumor.     

Extraperitoneal anterior approach to renal vessels in radical surgery of renal cancer

A 63-year-old female developed the chest wall tumor protruding into the right thoracic cavity. She consulted our hospital complaining of chest pain. 20 years before this episode, she had undergone tumor extirpation combined with the partial resection of adherent anterior chest wall and the diaphragm for large benign solitary fibrous tumor of the pleura. Because of the difficulty in making diagnosis by needle biopsy, operation (re-tumor extirpation combined with the chest wall) was done. Histological examination revealed that the tumor was malignant solitary fibrous tumor. We concluded that the tumor was the malignant recurrence of the benign solitary fibrous tumor resected 20 years before. Occasionally, benign solitary fibrous tumor of the pleura recurs and behaves more aggressively than primary, but such a long latent period as 20 years is quite uncommon. So we present the case and the review of the literature.     

A highly differentiated exocrine pancreatic tumour in a young boy

A primary pancreatic tumour in a 6-year-old boy was removed by radical excision. From both light and electron microscopic observations the tumour was considered to be of exocrine origin, with some differentiation towards acinar cells. Although the tumour was highly differentiated, it was regarded as probably malignant because of tumour growth into the surrounding fibrous capsule. The case is discussed in relation to earlier rare reports of pancreatic tumours in infants and children.     

Aneuploidy in atypical fibroxanthoma: DNA content quantification of 10 cases by image analysis

It has recently been reported that atypical fibroxanthoma (AFX) is a predominantly diploid lesion in contrast to malignant fibrous hystiocytoma (MFH) which is usually aneuploid. To test this hypothesis, DNA content quantification was undertaken on Feulgen-stained cytology and tissue section preparations from 10 cases of AFX by image analysis. The large atypical cells which characterize AFX were aneuploid in each case. Smaller spindle-shaped cells found in this lesion were diploid. The results suggest that AFX is indistinguishable from MFH by DNA content estimation and highlight an advantage of image analysis over flow cytometry.