Benign localized mesothelioma of the pleura

Eleven cases of benign localized mesotheliomas of the pleura are described. Ten patients were asymptomatic and discovered by routine X-rays. In eight cases the tumour was localized in the visceral pleura and all tumours showed only a benign mesenchymal component. Non-neoplastic epithelial structures can become entrapped within the tumour. A benign clinical behaviour and an excellent prognosis could be expected after surgical resection.     

Pleural mesothelioma of connective tissue type, localized fibrous tumour of the pleura, and reactive submesothelial hyperplasia. An immunohistochemical comparison

Ten diffuse pleural mesotheliomas of connective tissue type have been compared with 14 examples of pleural granulation tissue and 7 localized fibrous tumours of the pleura, using immunohistochemistry to identify cytokeratins of low and high molecular weight and vimentin. Low molecular weight cytokeratin and vimentin were both detected in 8 of the 10 mesotheliomas and in 12 of the 14 reactive lesions. High molecular weight cytokeratin was rarely detected in either lesion. The seven localized fibrous tumours of the pleura were all positive for vimentin and negative for both cytokeratins. These findings support an origin of connective tissue type mesotheliomas from multipotential submesothelial spindle cells and of localized fibrous tumours of the pleura from either conventional fibroblasts or resting submesothelial spindle cells. Antibodies to cytokeratin help distinguish these two neoplasms but provide no assistance in the more difficult diagnostic problem of distinguishing mesotheliomas of connective tissue type from pleural reactions characterized by abundant granulation tissue.     

Localized (solitary) fibrous tumor of the pleura

Clinical, light microscopic, ultrastructural, and immunocytochemical features of localized fibrous tumor of the pleura are reviewed. The differential diagnosis of the benign tumors can be uncomplicated, but atypical variants and malignant forms require the exclusion of other tumors included in the broad array of spindle cell neoplasms that can arise in or extend to a serosal surface. Electron microscopy is useful, but immunostaining procedures offer more extensive and reliable help in reaching the correct diagnosis. Tumors histologically similar to localized fibrous tumor of the pleura have been described in a number of extraserosal locations. Some localized fibrous tumors may be true fibromas, whereas the typical pleural tumor appears to arise from the subserosal mesenchymal cell and is composed of CD34-positive cells which are more primitive in their morphology than mature fibroblasts.     

Structural patterns and histological behaviour of experimental sarcomas. I. General considerations, histology and histochemistry.

Methylcholanthrene-induced rat sarcomas were used as a model for the examination of morphological and cytological differentiations in tumours of the connective tissue. Particular attention was paid to the question how far these sarcomas are comparable to human connective tissue tumours. The histological examination yields a broad spectrum of mesenchymal differentiations ranging from undifferentiated anaplastic sarcomas over less differentiated fibrosarcomas and malignant fibrous histocytomas to well-differentiated fibrosarcomas, myosarcomas and haemangiopericytomas. It is worth mentioning that different histological structures can be encountered with one and the same tumour.     

Mammary fibroadenoma and some phyllodes tumour stroma are composed of CD34+ fibroblasts and factor XIIIa+ dendrophages

Fibroadenomas and mammary phyllodes tumour arise by proliferation of mammary stroma and epithelial elements. However, it is the stromal element that determines the biology of these biphasic tumours. Normal mammary stroma, like most collagenous connective tissue, contains resident populations of CD34+ dendritic interstitial cells and scattered factor XIIIa+ collagen-associated dendrophages. Actin + myofibroblasts are usually absent from mammary stroma in non-disease states. To determine whether CD34+ and factor XIIIa+ cells proliferate in fibroadenomas and phyllodes tumours, and to study myofibroblastic differentiation in these lesions, we examined 19 fibroadenomas in 14 patients along with five low grade and two high grade phyllodes tumours. We employed antibodies against the human progenitor cell antigen CD34, coagulation factor XIIIa and HHF-35 actin. In three fibroadenomas and two phyllodes tumours, we used Ki-67 antigen to study cell proliferation and oestrogen and progesterone receptors to study possible hormonal influence on stromal cells. In all fibroadenomas, CD34 strongly stained interlobular, pericanalicular and intracanalicular fibroblasts with collagenous and/or myxoid features. Four low grade phyllodes tumours also had CD34+ fibroblasts as did one high grade tumour. Actin reactivity varied and was most pronounced in six fibroadenomas resembling the so-called cellular variant, while seven regular fibroadenomas had no actin + stromal cells and six had only focal and weak actin + stromal cells. Factor XIIIa+ cells were prominently admixed in the stroma of all tumours studied comprising from 5% to 20% in fibroadenomas and, focally, up to 50% in phyllodes tumours. Oestrogen and progesterone receptors were expressed only in glandular elements. Ki-67 index in stromal cells was 1% to 3% in fibroadenoma, 10% to 20% in low grade, and 20% to 40% in high grade phyllodes tumour. We conclude that fibroadenomas and some phyllodes tumours are composed of CD34+ fibroblasts that show varying myxoid, collagenous or myofibroblastic differentiation. The fibroblasts are accompanied by a subset of dendritic histiocytes that express factor XIIIa. Fibroadenoma variants show prominent collagenous actin + myofibroblastic differentiation of CD34+ stromal cells, sometimes with a gradient of CD34 down-regulation. Fine-needle or limited stereotactic core biopsy of these biphasic tumours, if they yield only stromal cells, must be distinguished from other CD34+ stromal tumours. Increased factor XIIIa+ dendrophage populations were seen in phyllodes tumours, especially in two high grade tumours that had malignant fibrous histiocytoma-like features, suggesting clonal evolution toward the fibrohistiocytic final pathway. Further study of CD34 and factor XIIIa + mammary stromal cells in larger numbers of phyllodes tumours might ascertain whether increasing factor XIIIa reactivity correlates with differentiation and increased tumour aggressiveness.     

Malignant fibrous histiocytoma of the lung

Summary A case of malignant fibrous histiocytoma of the lung is reported. The tumour margin was well circumscribed, showing an expanding border and no capsule. The main part of the tumour was composed of spindle-shaped fibroblast-like cells arranged in broad fascicles with a partially storiform pattern. Other parts of the tumour were arranged in a haphazard pattern, containing many mononucleated and multinucleated giant cells. Ultrastructurally six differnt cell types were encountered. The dominant type was a fibroblast-like cell; also present were many giant cells and some histiocyte-like cells, together with their intermediate forms, and few undifferentiated mesenchymal cells. We consider this tumour to have developed from the peribronchial connective tissue; it has the same cellular composition as the malignant counterpart arising in soft tissues.     

Cellular differentiation in storiform-pleomorphic malignant fibrous histiocytomas. An electron microscopic study of histogenesis

The most common form of malignant fibrous histiocytoma is the storiform-pleomorphic subtype composed of spindle-shaped fibroblast-like cells, mononucleated histiocytic elements and a changing amount of pleomorphic giant cells. In relation to the changing cellular structures 14 pleomorphic-storiform malignant fibrous histiocytomas were investigated electronmicroscopically. In all tumors several types of cells varying in shape, and size as well as in organelle composition could be demonstrated: 1. Undifferentiated cells, which are relatively small and have a scanty cytoplasm with few organelles. 2. Fibroblast-like cells with well developed rough endoplasmic reticulum, mostly arranged in a storiform pattern. 3. Myofibroblasts corresponding to fibroblasts and showing bundles of thin filaments (4 to 6 nm) with focal dense bodies in the peripheral area of the cytoplasm. 4. Histiocyte-like cells characterized by filopodia-like projections and abundant cytoplasm containing lysosomes and phagolysosomes and also lipid droplets. 5. Chimeric cells, which are intermediate forms with features of fibroblast-like and histiocyte-like tumor cells. 6. Multinucleated tumor giant cells which can be subdivided into fibroblast-like and histiocyte-like types and intermediate forms. On the basis of our ultrastructural studies the storiform pleomorphic malignant fibrous histiocytoma is interpreted as a tumor of an undifferentiated mesenchymal cell with the potency of fibroblastic or histiocytic differentiation. The origin of this cell is uncertain. Dedifferentiation of a differentiated connective tissue cell (fibroblast, pericyte) into a proliferating undifferentiated precursor cell is discussed.     

Solitary fibrous tumour of the renal peripelvis

Solitary fibrous tumours (SFTs) are rare spindle cell neoplasms generally associated with the serosal surface, especially the pleura. This report describes two SFTs arising in the renal peripelvis, occurring in 33- and 36-year-old females. The lesions lacked the characteristic features of other recognized neoplasms that occur in the kidney. Immunohistochemically, the tumour cells were diffusely and strongly positive for vimentin and CD34, and some tumour cells expressed alpha-smooth muscle actin. Both tumours were diploid by flow cytometry. Both patients have had benign clinical courses with 7.5- and 1-year follow-up. The findings suggest that the SFTs may originate from peripelvic mesenchymal cells, a new location for SFT. SFT should be included in the differential diagnosis of spindle cell tumours arising in the renal pelvis and peripelvis.     

Disseminated malignant solitary fibrous tumor of the pleura

Solitary fibrous tumor (SFT) of the pleura typically forms a localized pleura-based mass, and most are benign. A rare case of disseminated malignant SFT of the pleura is reported. The patient was a 71-year-old man who presented with complaints of shortness of breath to his primary care physician. A diagnosis of malignant mesothelioma was suspected, based on clinical, radiological and needle biopsy findings. He was referred to our institution for surgery. An extrapleural pneumonectomy, encompassing all pleural masses, was performed. Gross examination of the resected specimen was remarkable for numerous masses, ranging in size from 0.2 to 13.5 cm, covering the majority of the visceral pleura. Histologically, the tumor was composed of short spindle cells admixed with variable proportions of collagenous stroma. There were great intra- and intertumoral heterogeneity in tumor growth pattern, cellularity, pleomorphism and mitoses. Histologically malignant areas were present in all of the masses examined. The neoplastic cells were diffusely and intensely positive for bcl-2. Most tumor cells were also strongly stained for CD34 and CD99. Staining for cytokeratin was negative. The tumor also revealed p53 over-expression. Thus, the histological and immunohistochemical features of the tumor were consistent with a disseminated malignant SFT. This report shows that SFT rarely presents with disseminated pleural involvement, and a panel with CD34, bcl-2 and cytokeratin are valuable for differentiating SFT from malignant mesothelioma and other malignant spindle cell neoplasms of the pleura.     

Solitary fibrous tumour of the pancreas: a new member of the small group of mesenchymal pancreatic tumours

Solitary fibrous tumours usually occur in the pleura, but occasionally they appear in extraserosal soft tissues or parenchymatous organs, where their diagnosis often causes problems. This report describes a solitary fibrous tumour (SFT) of the pancreas in a 50-year-old woman treated by left-side pancreatectomy. The tumour showed immunocytochemical reactivity for CD34, CD99 and bcl-2. Because of its favourable prognosis, SFT must be clearly distinguished from leiomyosarcoma, the most frequent nonepithelial tumour of the pancreas. Other mesenchymal tumours that may occur in the pancreas include tumours of the peripheral nerve sheath, fibrous histiocytic tumours and rare vascular tumours. Received: 14 December 1998 / Accepted: 24 March 1999     

New marker for mesothelioma: an immunoperoxidase study.

An antibody was raised against a protein isolated from the cytoplasm of mesothelioma cells. It was subsequently used in an immunoperoxidase procedure on formalin fixed, paraffin embedded tissue sections. A representative sample of benign and malignant tumours from all the systems of the human body was examined. All the tumours derived from coelomic surfaces (mesotheliomas of pleura, peritoneum, and ovary, and adenomatoid tumour of epididymis) reacted with the antibody. No other tumour tested in this study expressed the protein. These findings indicate that the antibody may be useful in the identification of mesothelioma cells in both histological and cytological diagnostic routine practice when morphological interpretation is in doubt.     

Calcifying fibrous tumor of the adrenal gland

Calcifying fibrous tumor is an uncommon entity with distinctive pathologic features. Most calcifying fibrous tumors involve the peripheral soft tissues or serosal surfaces, with reports of visceral examples of this lesion being extremely limited. We report the clinical and pathologic features of an unusual case of calcifying fibrous tumor occurring in the adrenal gland of a 32-year-old woman. Microscopically, the lesion was well circumscribed and composed of dense, poorly cellular collagenous tissue, scattered spindle cells, an inflammatory infiltrate consisting of plasma cells and lymphocytes, and dystrophic calcifications. The morphologic diagnosis of calcifying fibrous tumor was supported by diffuse positive immunoreactivity for factor XIIIa and absence of reactivity for muscle specific actin, smooth muscle actin, and anaplastic lymphoma kinase. Although rare, awareness that calcifying fibrous tumor may occur at this particular site is important so as not to confuse this lesion with other mesenchymal neoplasms of the adrenal gland.     

Co-expression of cytokeratin and vimentin intermediate filament proteins in benign and neoplastic breast epithelium

This paper identifies another neoplasm of epithelial origin which may express vimentin in addition to cytokeratins, thereby adding to the expanding list of tumours which demonstrate intermediate filaments (IFs) other than those of their reputed cell of origin. Twenty examples of benign breast disease and 66 carcinomas were examined for vimentin and cytokeratin IFs using an avidin-biotin-peroxidase complex technique. Co-expression of these IF proteins was found in 35 per cent of cases of benign breast tissue and in 60 per cent of the carcinomas. In 8 (16 per cent) of 50 cases of infiltrating ductal carcinoma, vimentin and cytokeratin immunostaining was observed in more than 60 per cent of the tumour cells. These carcinomas were predominantly of a high histological grade. In benign breast disease and well-differentiated carcinoma, vimentin was distributed in the basal and perinuclear regions of the cells, with sparing of the apical portions. In those cases in which large numbers of tumour cells expressed vimentin, cytoplasmic staining was diffuse, and often exhibited distinctive perinuclear and subplasmalemmal accentuation. We propose that a knowledge of the list of carcinomas which may co-express vimentin and cytokeratin IFs might be helpful in the assessment of undifferentiated tumours and metastatic deposits.     

The ultrastructure of benign and malignant fibrous histiocytomas

Five benign histiocytomas of varying pattern and three malignant fibrous histiocytomas have been studied ultrastructurally. An essentially biphasic pattern of histiocytes and fibroblasts was present. In addition fibrohistiocytes, myofibroblasts and undifferentiated cells were present in some of the tumours. The histogenesis of this group of tumours is discussed. The value of electron microscopy in establishing the diagnosis in difficult cases is emphasized, but it is not considered useful in distinguishing benign from malignant cases.     

Ultrastructural findings supporting the angioblastic nature of the so-called adamantinoma of the tibia

Electron microscopy of a case of adamantinoma of the tibia shows features which support a mesenchymal angioblastic origin rather than epithelial. Comparison is made between tissue from this tumour and a squamous cell carcinoma of the femur arising in chronic osteomyelitis. In adamantinoma no desmosomes are found between tumour cells and their cytoplasmic ultrastructure shows features of mesenchymal cell type including evidence of pinocytic activity and bundles of filaments resembling hyperplastic endothelial cells. The stroma shows features similar to fibrous dysplasia of bone with fibroblasts, histiocytes and fibrolipoblastic lipid-laden mesenchymal cells. It is condluded that adamantinoma of the tibia should be considered to be an angioblastic tumour of bone.     

Malignant fibrous histiocytoma of bone associated with focal hemangiopericytomatous pattern

A case of malignant fibrous histiocytoma of the tibia of a 49-year-old Japanese farmer was presented. The patient was diagnosed as malignant hemangiopericytoma by biopsy, whereas the amputated material showed a marked pleomorphism representing features of malignant fibrous histiocytoma. Ultrastructurally, undifferentiated mesenchymal cells, intermediate cells between the undifferentiated mesenchymal cells and fibroblastic cells, fibroblastic cells and histiocytoid cells including bizarre giant cells were confirmed in a broad modulating spectrum. The hemangiopericytomatous lesion was predominated by intermediate cells, the ultrastructure of which bore a close resemblance to that of pericytes, and was regarded to be resulted from a differentiation of undifferentiated mesenchymal cells towards the pericyte.     

Low grade fibromyxoid sarcoma: clinicopathological analysis of eleven new cases in support of a distinct entity

Low grade fibromyxoid sarcoma is a recently recognized, uncommon soft tissue neoplasm with a tendency to develop in deep soft tissue of young adults. Diagnostic criteria have not been well defined and this tumour has not been widely accepted as a distinct entity. Eleven new cases are reported here for which reproducible histological features are described and in which the immunohistochemical profile of the tumour cells is documented for the first time. Ten of the eleven patients were male and the majority were young or middle-aged adults (median age 45 years). All except one of the tumours were situated in deep soft tissue. Lower limb (four cases) and chest wall (three cases) were the commonest primary sites; one case each arose in the groin, buttock, axilla and retroperitoneum. Follow-up (median duration 6 years) was available in nine patients. Six developed local recurrence and in five cases recurrences were multiple. Pulmonary metastasis occurred in one patient. All tumours were characterized by the presence of bland spindle cells, showing a mainly whorled or focally linear arrangement, set in alternating areas with a fibrous or myxoid stroma. Tumour cells were small, spindle to stellate, with poorly defined, palely eosinophilic cytoplasm and hyperchromatic ovoid nuclei. Most tumour cells showed strong staining with antibodies to vimentin, while occasional cells stained positively for actin, desmin and cytokeratin, in keeping with focal myofibroblastic differentiation. Ultrastructural examination in one case revealed features of fibroblasts. Careful consideration of the morphological and immunohistochemical features of these tumours permits a positive diagnosis of low grade fibromyxoid sarcoma and allows its distinction from a number of other benign and malignant soft tissue neoplasms.     

Expression of cell adhesion molecules and common acute lymphoblastic leukaemia antigen in hepatoblastoma

Hepatoblastoma is an embryonal tumour of the liver, which often contains tissue components with multidirectional differentiation. The occurrence of cell surface antigens in this tumour has not been studied systematically, and we therefore investigated 20 hepatoblastomas for the expression of common acute lymphoblastic leukaemia antigen (CALLA) and cell adhesion molecules (CAMs) in their different tissue components. Epithelial tumour cells of fetal differentiation contained E-cadherin. This protein did not occur in tumour areas with embryonal or mesenchymal differentiation. In contrast, immature embryonal and anaplastic cells expressed CALLA and the hyaluronate receptor (HCAM, CD44). Both fetal and embryonal areas stained irregularly positive for ICAM-1, which, in contrast, was not present on anaplastic cells. Immature fibrous tissue did not contain any of these molecules except for ICAM-1. However, some cells adjacent to, or enclosed in, osteoid were positive for HCAM and NCAM. Like small undifferentiated hepatoblastoma cells, primitive mesenchymal spindle-shaped cells also expressed CALLA, HCAM, and the polysialylated embryonic form of NCAM strongly. This last is not present on other epithelial or mesenchymal tumour cells. Hepatoblastoma cells of varying differentiation express distinct patterns of CAMs and CALLA. Our results give further insight into their histogenesis and cellular interactions and may explain their variable ability for invasive growth and formation of metastases.     

Multiple calcifying fibrous tumors of the pleura

Calcifying fibrous tumor (CFT) is a rare lesion characterized histologically by hypocellular hyalinized collagenous tissue with psammomatous and/or dystrophic calcifications and patchy lymphoplasmacytic infiltrates. CFT usually occurs in the somatic soft tissue of children and young adults but is rarely found in the pleura. We describe here an unusual case of multiple small CFTs in the right mediastinal pleura of a 54-year-old man who had a history of renal cell carcinoma. Suspecting pulmonary and pleural metastases, we performed wedge resection of the right middle lobe and local excision of two nodules in the right pleura. Light microscopy revealed metastatic lesions of renal cell carcinoma in the resected wedge. The pleural nodules were well circumscribed and composed of hypocellular, dense, hyalinized, collagenous tissue with scant lymphoplasmacytic infiltration and characteristic psammoma bodies. Immunohistochemical staining revealed that most spindle cells were positive for vimentin, CD34 and factor XIIIa, and negative for epithelial membrane antigen, keratin, smooth-muscle actin, desmin, S-100 protein and anaplastic lymphoma kinase. We made a histological diagnosis of CFT of the pleura, and the patient remains well 6 months after the wedge resection.