Pulmonary lipomatous hemangiopericytoma: report of a rare tumor and comparison with solitary fibrous tumor.

Lipomatous hemangiopericytoma is a rare mesenchymal tumor showing areas of lipid-containing cells admixed with a spindle-cell component. Like other hemangiopericytomas, it shows a similar vascular pattern to solitary fibrous tumor and, partly for this reason, it and other hemangiopericytomas have been subsumed into solitary fibrous tumor. The present study provides a comprehensive documentation of a single case of pulmonary lipomatous hemangiopericytoma of the lung, the first to be described at this site, and compares it with solitary fibrous tumor, in terms of clinical, histological, immunohistochemical, ultrastructural, and cytogenetic findings. Apart from the lipid-laden-cell component, pulmonary lipomatous hemangiopericytoma and solitary fibrous tumor were similar histologically. Bcl-2 was positive in both. CD34 was minimally expressed in pulmonary lipomatous hemangiopericytoma, which possessed some non-descriptive intercellular junctions, a feature shared by solitary fibrous tumor, which was CD34 positive. However, one of the latter was rich in gap junctions, a feature consistent with strong connexin (Cx) 43 staining and the existence, hitherto unappreciated, of a CD34/Cx43-positive tumor cell network. In pulmonary lipomatous hemangiopericytoma, chromosomal deletions of 43-44, X, -Y were found. In solitary fibrous tumor, 46, XY, del(13)(q?) abnormalities and abnormalities involving chromosome 10 were frequently observed. These similarities and differences are discussed in the context of the currently favored diagnostic fusion of hemangiopericytoma and solitary fibrous tumor.

Ultrastructural spectrum of solitary fibrous tumor: a unique perivascular tumor with alternative lines of differentiation.

Eight tumors diagnosed as solitary fibrous tumor (SFT) of the oral cavity were studied. Histologic spectrum was entirely comparable with the extrapleural SFT of other sites. One tumor had glomus tumor-like foci. Immunohistochemical results confirmed most of the previous observations, indicating characteristic expression of vimentin, CD34, bcl-2, and CD99. Factor XIIIa and alpha-smooth muscle actin were less commonly reactive and a very few cells were faintly positive for factor VIII-related antigen and Ulex europaeus agglutinin 1. All were essentially negative for S-100 protein, desmin, CD31, and CD68. In stark contrast to the conclusive immunoprofile, ultrastructural investigation of six tumors demonstrated considerable cellular heterogeneity. Other than fibroblasts, perivascular undifferentiated cells and pericytes predominated, but endothelial cells were regularly present. There was a distinctive proliferation of pericytic cells in four tumors, one of which had glomoid foci of myopericytes. The extreme increase in number of Weibel-Palade bodies occurred in voluminous capillary endothelium. Occasional single and clustered cells with consistent features of endothelium showed intracytoplasmic lumen formation. Such composite cells constituted an integral segment of richly vascularized SFT. Myofibroblastic form smooth muscle differentiation was present in only a minority of cells. From phenotypic analysis by electron microscopy, SFT may originate from a unique, perivascular multipotent mesenchyme sharing with its lineage with pericytes, fibroblasts, and infrequently, endothelium. Consequently, morphological features of SFT may become diversely varied by whether predominantly constituent cells are undifferentiated, pericytic or fibroblastic in nature.

Intracellular collagen and fibronexus in fibromatosis and other fibroblastic tumors.

Myofibroblasts are mesenchymal cells with combined function and structure for contraction and collagen synthesis. They are found in reparative responses, nodular fasciitis, fibromatosis, and myofibroblastic sarcoma. Ultrastructurally, myofibroblasts are characterized by a specialized cell surface structure called the fibronexus (FNX). In addition, intracellular collagen fibers (ICF) have been described in nodular fasciitis and fibromatosis, but their origin and nature are still controversial. The aim of the present work was, first, to assess the frequency of FNX and ICF in proliferative myofibroblastic conditions compared to diverse mesenchymal tumors with spindle-shaped cells, and, second, to determine what kind of organelles contain ICF and if they are related to phagocytosis or cell synthesis. Forty-two cases of aggressive fibromatosis and 11 of nodular fasciitis (group A) were compared to 82 spindle-cell mesenchymal tumors of diverse nature (group B) by electron microscopy study. The presence and frequency of FNX and ICF was compared in both groups, and the organelles containing ICF were recorded. FNX and ICF were constantly found in group A (69.8 and 84.9%, respectively), and rarely in group B (0 and 5.12%, respectively). Most frequently ICF were contained in tunnels and phagolysosomes, but also were found in Golgi vesicles and cisternae of rough endoplasmic reticulum. In the majority of cases (75%), ICF were similar to collagen fibers of the extracellular space, but in some cases (22.5%), they were in dissimilar stages of fibrogenesis. Fibromatosis and nodular fasciitis are characterized by proliferation of myofibroblasts and constantly show FNX and ICF. These structures are rarely found in other mesenchymal tumors. The ICF are found in organelles of digestion and also in others related to synthesis and transport.

The spectrum of pediatric fibroblastic and myofibroblastic tumors.

Fibroblastic and myofibroblastic tumors in neonates, infants, and children provide a diagnostic dilemma in surgical pathology due to their relative rarity and similarity in appearances. These tumors may be congenital or occur early during the first years of life or later during the first and second decades of life. The morphologic, immunocytochemical, ultrastructural, cytogenetic, and molecular features of the more "common" pediatric fibroblastic and myofibroblastic tumors are reviewed. In addition, the importance of a multimodal approach to tumor diagnosis is emphasized, with correlation with treatment and outcome differences among these unique fibroblastic and myofibroblastic tumors. The importance of providing an accurate diagnosis with pediatric fibroblastic and myofibroblastic tumors cannot be overstated, because treatment, prognosis, follow-up, and outcome are based on the initial assessment of these fascinating, but oftentimes, perplexing tumors.

Fibroblast phenotype plasticity: relevance for understanding heterogeneity in "fibroblastic" tumors.

Cellular transformations, reflecting phenotypic plasticity, characterize embryonic life, would-repair, physiological adaptation, and neoplasia. Fibroblastic tumors show a range of cellular differentiation, which can be rationalized in terms of phenotypic plasticity of the "normal" fibroblast. In this paper, the various kinds of fibroblast transformation are discussed, and some insights provided into the molecular mechanisms involved. Comparable molecular events may take place in neoplastic fibroblasts to produce the heterogeneous tumors nevertheless identified as fibroblastic. The following transformations are discussed: histiocytic, and fibrohistiocytic tumors; adipocytic, and lipogenic tumors; myofibroblastic, and myofibroblastic tumors. A definition of the fibroblast is required. This consists of spindle-cell morphology, vimentin-staining, and abundant rough endoplasmic reticulum. Transformation to histiocytic, lipogenic and myofibroblastic phenotypes requires the development of lysosomes, lipid droplets and lamina, and peripheral myofilaments and fibronexuses respectively. These occur in non-malignant transforming (transdifferentiating) fibroblasts, and also in tumors identified as fibrohistiocytic, lipogenic and myofibroblastic. The molecular basis of the myofibroblast transformation is probably the best studied. It is driven primarily by transforming growth factor beta. Investigations into the mechanisms of differentiation in normal fibrobiasts could prove fertile ground for defining comparable differentiation in tumors. In this respect, there are very few publications on the presence of growth factors in tumors or tumor-like lesions. There is, however, increasing investigation into gene expression and gene products in tumors, which bear on the differentiation process. Ultimately, our understanding of the molecular events controlling differentiation in cancer will lead to control, cure and prevention.

Solitary fibrous tumor of the abdominal wall: a report of two cases immunohistochemical, flow cytometric, and ultrastructural studies and literature review.

Solitary fibrous tumors have been described at many extrapleural sites in recent years. However, solitary fibrous tumors arising from somatic soft tissue occur only rarely and can pose problems in the differential diagnosis from other benign or malignant soft tissue tumors. The majority of solitary fibrous tumors occurring in the somatic soft tissue have been found in the extremities and limb girdles, and the head and neck regions. There have been only eight published cases located in the abdominal wall. We herein report two female patients who developed solitary fibrous tumors of the abdominal wall that were not in association with the underlying peritoneum. Histologically, both tumors were characterized by a variety of architectural patterns, alternating hypercellular and hypocellular areas, proliferation of plump spindle cells, thick keloid-like and/or amianthoid collagen bundles, and ectatic staghorn-like vessels. Both tumors showed a diffuse strong reaction for CD34 and vimentin as well as focal positivity for bcl-2 and smooth muscle actin. A striking predominance in females was found in a literature review of solitary fibrous tumors of the abdominal wall, contrasting with other somatic soft tissue sites which show an equal gender distribution. Interestingly, expression of estrogen but not progesterone receptor was observed in both tumors. Ultrastructurally, the tumor cells displayed features of fibroblasts with dilated branching rough endoplasmic reticulum (RER) and Golgi apparatus. Both tumors assayed by flow cytometry demonstrated a diploid DNA content with an S-phase fraction of 7.9% and 11.4%, respectively. At follow up, both patients were well without evidence of recurrence or metastasis after surgical excision.

June 2001: 61 year old woman with confusion and obtundation.

The June COM. A 61 year old female presents with a three week history of increasing confusion, lethargy and headache. A neurological exam revealed disorientation, mild expressive aphasia, bilateral papilledema, and a right pronator drift. She had a craniotomy and resection of tumor. The tumor histologically was consistent with a solitary fibrous tumor displaying malignant features of hypercellularity, marked nuclear atypia, high mitotic activity, and a high proliferation index. This case is unique as the first malignant variant of solitary fibrous tumor to be reported intracranially.

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.

Role of electron microscopy in the evaluation of soft tissue neoplasms, with emphasis on spindle cell and pleomorphic tumors.

The current significant role of transmission electron microscopy in the evaluation of soft tissue tumors when correlated with conventional histological and immunohistochemical studies is discussed for the following entities: myxofibrosarcoma, storiform-pleomorphic fibrosarcoma (malignant fibrous histiocytoma), and myofibrosarcoma; dermatofibrosarcoma protuberans; hemangiopericytoma; monophasic synovial sarcoma; extrarenal rhabdoid tumor; soft tissue perineurioma; and gastrointestinal stromal tumors, notably the so-called autonomic nerve variant.

Solitary fibrous tumour: clinicopathological, immunohistochemical, and ultrastructural analysis of 12 cases arising in soft tissues, nasal cavity and nasopharynx, urinary bladder and prostate.

The clinicopathological features of 12 extraserosal solitary fibrous tumours (SFT) are described. The age of the patients ranged from 18 to 72 years (mean: 48.2 years; median: 54 years); 5 were female patients. Seven lesions arose in soft tissue (5 in perifascial, and 1 each in subcutaneous and intramuscular tissues). They were situated in the groin (2 cases) and the neck, right buttock, left scapula, upper arm, and anterior abdominal wall (1 case each). One polypoid lesion was seen in in the nasal cavity and 1 in the nasopharynx; 2 neoplasms arose in the urinary bladder and 1 was located in the prostate and periprostatic tissue. Nine lesions were excised; in 1 patient wide excision was performed and in 2 patients, transurethral resection. Limited follow-up of 3 cases revealed a benign clinical course. The size of the neoplasms ranged from 1.7 cm to 20.0 cm (mean: 5.4 cm; median: 3.5 cm). Histologically, the neoplasms were well circumscribed and composed of cytologically bland spindle cells arranged without an obvious pattern; focally storiform or fascicular growth patterns were seen. Tumour cells were separated by thick bands of collagen demonstrating foci of keloid-like hyalinization. Prominent vascularity showing a haemangiopericytoma-like vascular pattern and vessels with thick, hyalinized vessel walls were seen in all cases. Increased mitotic activity was noted in 2 soft tissue cases (4-6 mitoses in 10 high-power fields); the other cases showed fewer than 2 mitotic figures in 10 highpower fields. Immunohistochemically, all cases tested stained positively for vimentin, CD34 and CD99, and 2 cases showed focal myofibroblastic differentiation. Two cases examined ultrastructurally showed a fibroblastic phenotype; focally pinocytic vesicles and microfilaments were identified. SFT represents a distinct neoplasm that should be included in the differential diagnosis of spindle-cell neoplasms in soft tissue, nasal cavity and nasopharynx, urinary bladder, and prostate. Strict diagnostic criteria are necessary to avoid overdiagnosis or confusion with more aggressive neoplasms in these locations.

Extrapleural solitary fibrous tumor: a report of seven cases.

Solitary fibrous tumors (SFTs) are rare, spindle-cell neoplasms generally associated with the serosal surface, especially the pleura. Histopathologic, immunohistochemical, ultrastructural, and flow cytometric analyses were performed on seven SFTs of extrapleural sites (two retroperitoneal, two soft tissue, one each peritoneal, nasal cavity, and orbit). Five patients were women, and two were men, aged from 21 to 68 years (average, 39 yr). All of the lesions presented as well-circumscribed masses. The lesions ranged in size from 2 to 20 cm in greatest diameter. Histologically, these lesions were entirely comparable to the pleural SFTs and lacked the characteristic features of other recognized neoplasms that occur in these regions. One tumor contained pleomorphic and round-cell sarcomatous foci. Immunohistochemically, all of the tumors were strongly positive for vimentin and CD34. Six of the seven tumors showed varying numbers of spindle cells positive for alpha smooth muscle actin, HHF35, neuron-specific enolase, Leu 7, or glial fibrillary acidic protein. Ultrastructural examinations of three tumors showed that they were composed of primitive mesenchymal or fibroblast-like cells. Six tumors examined were diploid by flow cytometric examination. Clinical follow-up in six patients ranged from 1 to 7.5 years (average, 2.6 yr) and showed that five patients remained well with no evidence of disease after excision and that the patient with the sarcomatous elements died of recurrence 2.5 years after surgical treatment. These findings suggest that SFTs represent ubiquitous neoplasms of fibroblasts or primitive mesenchymal cells with aggressive potential.

Tumor fibroso pleural: estudio inmunohistoquímico y ultraestructural de 14 casos / Fibrous tumor of the pleura: immunohistochemical and structural study of 14 cases

Se revisaron los casos de tumor fibroso pleural diagnosticados en nuestro Departamento en el período enero 1983-marzo 1994. Se obtuvieron 14 casos de los cuales 8 fueron mujeres y 6 hombres. El promedio de edad fue de 48.6 años con un rango de 27 a 82 años. Macroscópicamente, todos correspondieron a nódulos bien delimitados, de 1 a 15 cm. de diámetro mayor. Histológicamente,todos presentaron predominio de células fusadas, dispuestas en haces arremolinados, con fibrosis; menos frecuentemente, áreas hemangiopericitomatosas (2 casos) y mixoides (un caso). En un caso se encontraron inclusiones glandulares intratumorales de tipo bronquiolo-alveolar. El índice mitótico fue de 0, excepto en un caso donde se encontró una mitosis en 10 campos de aumento mayor. El estudio inmunohistoquímico con anticuerpos monoclonales demostró reacción positiva para vimentina en todos los casos y negativa para desmina y factor von Willebrand; sólo 2 casos (16.6 porciento) mostraron positividad para actina y uno de ellos para reacción positiva para citoqueratina (AE1 y AE3; 8.3 porciento). La microscopía electrónica realizada en 4 casos reveló células tumorales con caracteres de fibroblastos y miofibroblastos con ausencia de desmosomas. El tumor fibroso pleural es un tumor pleural benigno, aparentemente originado de células submesoteliales

Malignant solitary fibrous tumor of the pleura.

We describe a case of malignant solitary fibrous tumor of the pleura in a 15-year-old female who presented clinically with back pain. Grossly, the tumor had a pedicle attached to the pleura and histologically showed proliferating spindle-shaped cells with a high mitotic index. Immunohistochemical and ultrastructural features were consistent with a tumor of fibroblastic origin. Flow cytometric DNA analysis revealed an aneuploid population among the tumor cells.