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Some view ultrastructure as key to myofibrosarcoma diagnosis, whereas others argue that electron microscopy is too little used in contemporary practice to be considered an important diagnostic tool. These views are discussed in the context of 10 ultrastructurally confirmed cases of myofibrosarcoma, some occurring at rare sites such as skin and penis. Patient age ranged from 21 to 83 years, with a 6:4 male to female ratio. Size ranged from 2 to 7.5 cm and all had infiltrative margins. Histologically, all consisted of variably cellular fascicles of spindle cells with mild to moderately pleomorphic nuclei, small punctate nucleoli, and eosinophilic cytoplasm. All cases showed α-smooth muscle actin positivity and 2 showed very focal weak positivity for desmin. Ultrastructurally, the tumor cells contained rough endoplasmic reticulum, mainly peripheral smooth-muscle myofilaments, and fibronectin fibrils or fibronexus junctions at the cell surface. The most confident diagnosis of myofibrosarcoma is provided by ultrastructural examination. However, given the right histological appearance, use of a panel of antibodies that includes α-smooth muscle actin, desmin, and h-caldesmon, serves as an acceptable practical way of diagnosing myofibrosarcoma. [ABSTRACT FROM PUBLISHER]

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the gut. It is characterized by positive immunostaining for CD117, and bears mutations in the c-kit or PDGFRA genes. Its origin remains uncertain. GISTs mainly possess primitive smooth muscle or neuronal differentiation. Although an epithelioid pattern of GIST is a common finding on light microscopy, true epithelial differentiation has never been demonstrated by either immunohistochemistry or ultrastructural study. Here the authors report an epithelioid GIST of the stomach, immunopositive for CD117, DOG1.1, CD34, and PDGFRA, with slight cytoplasmic staining for epithelial membrane antigen. One heterozygous mutation on codon 842 of exon 18 of the PDGFRA gene was also found. Ultrastructurally, tumor cells had plentiful organelles, including some membrane-bound, dense-core granules and cytoplasmic vacuoles. Intermingled thin cellular processes were also found. Unusually, there were many structures resembling glandular epithelial intracellular lumina with processes. The processes, although resembling microvilli, did not have filament cores, while the lumina were either empty or contained some dense or flocculent content of uncertain nature. True intracellular lumina are very rare in GIST and the authors present findings related to this issue, with a discussion on their nature, origin, and significance. [ABSTRACT FROM AUTHOR]

An unusual case of intraparenchymal myofibromatosis of the brain occurring in a 29-year-old woman is described. Preoperative CT and MRI examinations revealed two well-circumscribed nodular masses localized in the wall of the left lateral ventricle and right temporal lobe, respectively. Both masses were completely resected, and the patient remains disease-free 2 years post-surgery. Histopathologically, the lesions were characterized by stratification. From outer to inner, there was a reactive glial component, lamellated well-differentiated muscle-like cells, densely compact collagen fibers and cellular tumor with nodular and hemangiopericytoma-like patterns, respectively. The myofibroblastic nature of this tumor was verified by immunohistochemical staining and ultrastructural analysis. Intraparenchymal myofibromatosis may be confused with, and should be distinguished from, meningioma, myopericytoma, solitary fibrous tumor, leiomyoma and inflammatory myofibroblastic tumor for accurate diagnosis and optimal treatment. [ABSTRACT FROM AUTHOR]

Sclerosing epithelioid fibrosarcoma (SEF) is a rare variant of fibrosarcoma, described initially by Meis-Kindblom et al. in 1995 (Meis-Kindblom JM, Kindblom L-G, Enzinger FM. Sclerosing epithelioid fibrosarcoma: a variant of fibrosarcoma simulating carcinoma. Am J Surg Pathol. 1995;19:979–993): more than 80 cases have been documented clinicopathologically since. Bone is a rare primary site for SEF, with only 2 cases so far reported. This paper documents the detailed clinical, histological, immunohistochemical, and ultrastructural features of a case occurring in the pubic bone of a 57-year-old diabetic woman presenting with a history of pain and compromised mobility involving her hip. Radiology revealed a destructive lesion in the right pubic bone. The lesion was resected, and 7 months postoperatively it recurred. The patient died following metastases to multiple bony sites and liver, some 4 years after the onset of symptoms. Histologically, the tumor was consistent with SEF, although it showed some anomalous immunostaining, which, however, is typical of the tumor (for example, for S-100 protein and epithelial membrane antigen). By electron microscopy, some rough endoplasmic reticulum was present, but also tonofibrils and desmosomes. The overall features were of an SEF with the ultrastructural but incomplete immunohistochemical evidence for divergent epithelial differentiation. The differential diagnosis of this tumor is discussed. [ABSTRACT FROM AUTHOR]

Rhabdomyosarcoma has traditionally been subclassified into alveolar, embryonal, and pleomorphic variants. Less commonly, spindle-cell, neuroendocrine, sclerosing, and lipid-rich or clear-cell subtypes are seen. The author recently encountered a myogenic sarcoma, with all the common markers of rhabdomyosarcoma, but expressing the unusual features of α-smooth-muscle actin and abundant rough endoplasmic reticulum (rER). This myogenic sarcoma, therefore, exhibited four lines of differentiation, and is documented here. The patient was a 65-year-old man with an inguinal soft tissue mass. Following surgical excision, the patient was given radiotherapy and was well without disease after 6 years. The tumor was positive for vimentin, desmin, α-smooth-muscle actin, α-sarcomeric actin, myogenin, MyoD1, and CD68. Cytoplasm was dominated by abundant rER intermingled with lipid droplets and lysosomes. Cell surfaces exhibited microvillous processes and focal adhesions, but no lamina. Subplasmalemmal smooth-muscle-type myofilaments with focal densities and rare sarcomeric filaments were seen. The low level of expression of some markers was interpreted as consistent with a poorly differentiated tumor. Given the four lines of differentiation—striated muscle, smooth muscle, fibroblastic, and histiocytic—a name reflecting its phenotype would be pleomorphic rhabdomyosarcoma showing smooth-muscle and fibrohistiocytic differentiation. [ABSTRACT FROM AUTHOR]

Primary and metastatic carcinomas have a reactive stroma characterized by many myofibroblasts. These cells have also been documented in nonepithelial malignancies, such as sarcomas, malignant melanoma, and lymphoid tumors but in generally far fewer numbers. In non-Hodgkin's lymphoma, Hodgkin's disease, and leukemia, myofibroblasts are rather rarely documented. In particular, there appear to be no reports of myofibroblasts in either primary bone-marrow/peripheral blood leukemia or secondary deposits of leukemia. In this paper, a case of a relapsed chronic myeloid leukemia appearing in an inguinal lymph node is described, containing many myofibroblasts. The case is detailed and presented with a discussion on the role of myofibroblasts in the progression of nonepithelial cancers. [ABSTRACT FROM AUTHOR]

Epithelioid sarcoma is an uncommon but well-described malignancy, which is found predominantly in the soft tissues of the young and middle-aged, and which pursues an indolent to aggressive course. It shows a degree of both mesenchymal and epithelial differentiation. Myofibroblastic differentiation has been recorded in epithelioid sarcoma for some time, the evidence being based mainly on the presence of smooth-muscle-type myofilaments and, more recently, on α-smooth-muscle actin and muscle-specific actin immunostaining. Myofibroblastic differentiation based on the stricter criterion of the fibronectin fibril/fibronexus junction has not so far been demonstrated except for a single atypical case with spindle-cell morphology and a cytokeratin-negative immunophenotype. The authors describe a conventional epithelioid sarcoma showing myofibroblastic differentiation based on the presence of fibronectin fibrils and fibronexus junctions. The patient was a 35-year-old Chinese male with a tumor that initially developed on his left forefinger: it recurred, then metastasised first to the left arm and eventually to the scalp. Histologically, the tumors had the typical features of epithelioid sarcoma: by immunohistochemistry, cytokeratin, epithelial membrane antigen, and vimentin were positive. By electron microscopy, rough endoplasmic reticulum, intermediate filaments, peripheral myofilaments, and fibronexus junctions were observed. This is the first epithelioid sarcoma of conventional histological type to show myofibroblastic differentiation on the basis of the more stringent criterion of the fibronexus. The findings are discussed in relation to the unusually varied differentiation reported for this tumor. [ABSTRACT FROM AUTHOR]

The fibronexus is recognized as a characteristic marker of the myofibroblast. However, it is not completely specific for this cell, having been seen in aortic smooth muscle (in attenuated form) and endothelium in experimental animals. This paper documents fibronexus junctions in human in vivo endothelium. Ultrastructural observations were made on the vasculature of a desmoplastic and focally neurotropic malignant melanoma. Cross-sectioned fibronectin fibrils were seen outside the stromal surface of the endothelial plasmalemma. Often, they were positioned directly opposite the actin-filament bundles in the peripheral cytoplasm. Neoplastic and in vitro cultured cells apart, endothelium is the only nonmyofibroblastic cell type to show well-developed fibronexus junctions. Mostly, they have been documented in aortic endothelium in experimental animals, where they possibly constitute an adaptation to hemodynamic stress, and where they might more securely anchor endothelium on to subjacent connective tissue. They might also function as mechanotransducers of extracellular stress in the extracellular milieu. The present observations constitute a further, rare example of endothelium-associated fibronexuses in reactive human vessels. [ABSTRACT FROM AUTHOR]

Basal/external lamina is not found over plasma cells or other hemolymphoid cells, and the feature can have diagnostic value in distinguishing the neoplastic counterparts of such cells from epithelium, endothelium, mesothelium, and so on, which do have this feature. In this paper, a material ultrastructurally indistinguishable from basal or external lamina is reported on reactive plasma cells found in a fibrous pseudotumor, intralobular stroma of normal breast, tumor stroma of squamous cell carcinoma, and submucosa of normal human small intestine. It was focal, followed the contours of the cell-surface membrane, was lightly textured, 40-80 nm thick, and separated from the plasma cell surface membrane by a clear space resembling a lamina lucida. Its function remains uncertain, although it may implement adhesion to other cells, as part of the immune functions that plasma cells and other hemolymphoid cells perform in the gut, for example, and elsewhere. [ABSTRACT FROM AUTHOR]

Lymphoma diagnosis rarely needs electron microscopy (EM), but one area where it can be useful is in the distinction of cytokeratin-positive lymphoma from carcinoma. The authors describe such a case, where difficulties were encountered due to lack of antibody specificity, distinguishing reactive from tumoral cells, and suboptimal sampling for EM. The tumor was in a lymph node next to the right submandibular gland in a 69-year-old man. This was a malignant tumor, composed of sheets of monomorphic large round cells. Interpretation on the part of a team of pathologists who examined this tumor was divided. On histological sections, the differential diagnosis was between carcinoma and lymphoma, which was modified to cytokeratin-positive lymphoma versus carcinoma since tumor cells were found to be cytokeratin-positive. EM of tumor retrieved from formalin showed plasmablastic features, in keeping with lymphoma with plasmablastic differentiation, one of the light microscopy diagnoses. The moderately strong positivity of cytokeratin and the positivity for Ber-EP4, however, supported carcinoma, and further sampling for EM was carried out, specifically on a cytokeratin-positive area of the wax block. Tonofibrils were found, supporting carcinoma. The final diagnosis was undifferentiated carcinoma with unknown primary site. The study emphasizes the need to take into account the imperfect specificity of cytokeratin, which can be found in several hemolymphoid neoplasms, to distinguish reactive from neoplastic cells, and to secure appropriate sampling for EM. This is one of the occasions where dewaxing (of an immunohistochemically defined wax block) offers positive advantages, despite compromised structural preservation, in the search for diagnostically important organelles. [ABSTRACT FROM AUTHOR]

The authors report a case of low-grade retroperitoneal malignant peripheral nerve sheath tumor (MPNST) showing Schwannian and fibroblastic differentiation in individual tumor cells. The tumor was detected in a 29-year-old male and posed diagnostic difficulty because of the unusual morphologic and immunophenotypic features. Morphologic examination of the H&E sections revealed a rather circumscribed, highly vascular, moderately cellular spindle cell tumor. The neoplastic cells were arranged in vague, short fascicles, distributed haphazardly amid hemangiopericytoma-like vascular channels, and showed occasional whorls. Myxoid stroma and keloid-like collagen bundles were frequently seen. There were satellite nodules outside the main tumor mass and low mitotic activity but no necrosis. The tumor cells stained strongly and diffusely for both S-100 protein and CD34. Electron microscopy revealed cells with processes and focal lamina, and prominent rough endoplasmic reticulum. Although the capacity of MPNST to exhibit divergent differentiation is well known, fibroblastic differentiation is generally poorly and inconsistently documented. The present case represents an unambiguous demonstration of the co-expression within individual tumor cells of Schwannian and fibroblastic differentiation in a low-grade MPNST. The literature on this subject is reviewed. [ABSTRACT FROM AUTHOR]

Rectal/anorectal malignant melanomas are highly aggressive tumors with a poor prognosis and low 5-year survival rate. They are also very rare. Of the well-known histological variants of malignant melanoma, the small cell subtype is also very uncommon; consequently, small cell anorectal malignant melanoma is an exceedingly rare occurrence. In this article, the authors provide a detailed clinicopathological description of small cell malignant melanoma of the rectum, documenting clinical, histological, immunohistochemical, and ultrastructural features, to add to the sparse references on this tumor in the literature. The patient was a 53-year-old woman with a mass 2 cm from the anus, which was surgically removed. In histological sections, the tumor was a small cell malignant melanoma, with a tumor cell diameter of 7.6±1.0 µm, and a range of 5.5-10.7 µm (N = 100). Tumor cells were positive for S-100 protein and HMB-45 and contained sparse but unambiguous type II melanosomes. This article is one of the few detailed clinicopathological documentations of a small cell malignant melanoma of the rectum (anorectum) and the first to have the diagnosis confirmed ultrastructurally by the identification of melanosomes. The present case adds to the 3 mainly or entirely small cell anorectal malignant melanomas described in the literature. There are also at least 12 other cases with less well-defined numbers of small tumor cells or with small cells admixed with other cell morphologies. Documentation of these unusual morphological variants is important for identifying any distinctive outcome they might exhibit compared with conventional malignant melanoma. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Pancreatic microcystic serous cyst adenomas are rare exocrine tumors composed of small cysts lined by glycogen-rich cells. The disease may be sporadic or present as part of von Hippel-Lindau (VHL) syndrome. Four sporadic cases of pancreatic serous cyst adenoma were examined by conventional histological, immunohistochemical, and ultrastructural methods. In the present study, new findings include the immunohistochemical identification of vascular endothelial growth factor (VEGF) and the lack of PDX-1 (putative master transcriptional factor in pancreatic stem cells) in the epithelial tumor cells. Ultrastructurally, many small blood vessels were intimately associated with epithelial tumor cells and adjacent fibroblastic cells. The observations suggest the possibility that VEGF-containing tumor cells act in a paracrine fashion to stimulate neovascularization; that peripheral blood in the vascular lumen might be filtered or processed by the endothelial and epithelial tumor cells; and that filtrates might therefore be stored as serous inclusions. It is hypothesized that pancreatic serous cyst adenomas might be under the abnormal regulation of the VHL gene, just like VHL disease itself and certain types of renal cell carcinoma, showing the distinctive histology of a rich vascularity intimately related to epithelial lining cells of cysts accompanied by stromal fibroblasts/myofibroblasts and collagenous stroma. [ABSTRACT FROM AUTHOR]

A case of metastatic malignant melanoma exhibiting small cell morphology is described. The patient had had a previous primary nodular small cell melanoma. The metastatic tumor was examined by conventional histology, light microscope immunohistochemistry, conventional electron microscopy, and ultrastructural immunolabeling. It consisted of small cells, which, however, varied in size and were present in distinct but merging areas. Tumor cells were negative for S-100 protein and very focally positive for cytokeratin: these findings in combination with small cell morphology suggested the possibility of small cell carcinoma. However, other melanocytic markers were positive. Neuroendocrine markers were negative. By electron microscopy, tumor cells lacked unambiguous melanosomes but contained paranuclear aggregates of nondescript granules. Following ultrastructural immunolabeling, these were found to be decorated with gold-labeled HMB-45 antibodies, thereby confirming them as lattice-deficient melanosomes. This tumor is an uncommon example of malignant melanoma where immunoultrastructural analysis helped clarify the nature of otherwise nondescript granules as true but lattice-deficient melanosomes. This is also the first case of small cell melanoma to he studied by electron microscopy. [ABSTRACT FROM AUTHOR]

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 ft Investigations into the mechanisms of differentiation in normal fibroblasts 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. [ABSTRACT FROM AUTHOR]

Cytotoxic therapy in young women with cancer may cause loss of ovarian function, and ovarian cryopreservation has been proposed as a means of preserving fertility. The objective of this study is to assess ultrastructural preservation of follicles in frozen–thawed ovarian cortical strips, previously cryopreserved using dimethylsulfoxide and a standard slow-cool/rapid-thaw protocol. Ovarian cortical strips(patients,n  =  7)were thawed and fixed in glutaraldehyde for epoxy resin embedding electron microscopy according to conventional procedures. Oocytes were generally well preserved, on the basis of plasma–membrane integrity, uniformity of chromatin pattern, mitochondrial and rough endoplasmic reticulum(rER)cisternal integrity, and absence of cytoplasmic and intranuclear clear spaces. Frequently, rER cisternae were distended and intramitochondrial matrices lost. Granulosa cells showed somewhat variable preservation. Some were dark-staining; others exhibited washed-out cytoplasm containing damaged or artifactually expanded organelles. The consistently good preservation of oocytes and the good but more variable preservation of granulosa cells provides scientific validation of one component in the overall clinical procedure of attempting to reestablish fertility in young female patients after cytotoxic therapy for cancer. [ABSTRACT FROM AUTHOR]

Although the histopathological subtypes of meningioma do not themselves appear to have prognostic significance, they are collectively important for defining the overall histopathological entity of microcystic meningioma(MCM)and allowing a distinction from other intracranial tumors, such as capillary hemangioblastoma, glioma, and metastatic renal cell carcinoma showing similar histology. Four cases of MCM were analyzed by conventional histology, immunohistochemistry, and electron microscopy. The present series of MCM was characterized by spindle- or cobweb-shaped tumor cells, characteristically associated small blood vessels, and a peculiar microcystic pattern. Among the microcystic meningeal tumor tissue, small areas of conventional subtypes were identified. Immunohistochemically, tumor cells showed the mesenchymal features of vimentin positivity and a rich distribution of matrix proteins around tumor cells. They lacked epithelial marker positivity but were faintly EMA positive. Ultrastructurally, primitive cellular junctions, desmosomes, and gap junctions were frequently seen between tumor cells. The gap junctions correlated with connexin 26 immunoreactivity. Although lacking an obvious epithelial nature, these features could be interpreted as showing an abortive differentiation mimicking meningothelial(arachnoidal)cells, which, physiologically, regulate cerebrospinal fluid between blood vessels and brain parenchyma. [ABSTRACT FROM AUTHOR]

An unusual leiomyosarcoma in the thigh of a 53-year-old woman is described. Tumor cells were spindled and positive for muscle immuno-markers. Some cells exhibited typical smooth-muscle ultrastructure - abundant myofilaments, focal densities, attachment plaques, plasmalemmal caveolae, and lamina. Others had fewer myofilaments and prominent rough endoplasmic reticulum. These features indicated a variable phenotype that included synthetic-phase (matrigenic) differentiation. Synthetic-phase cells were distinguished from myofibroblasts by typical smooth-muscle surface features in the absence of fibronexus junctions. In a subset of cells myofilaments were absent, but structures resembling solitary focal densities were identified. These are discussed as possible indicators of a primitive level of smooth-muscle differentiation. [ABSTRACT FROM AUTHOR]

Eighty-two mesenchymal tumors of the gastrointestinal tract were examined by electron microscopy for the purposes of subtyping for diagnostic precision and of understanding cellular differentiation. Tumors were subclassified into leiomyoma/leiomyosarcoma, tumors of the interstitial cell of Cajal (equivalent to traditionally defined GISTs [Miettinen et al. Hum Pathol. 1999; 30:1213-1220; Mod Pathol. 2000; 13:1134-1142]), gastrointestinal autonomic nerve tumors (GANTs), and fibroblastic and myofibroblastic tumors, using criteria from the literature. Leiomyoma/leiomyosarcoma were diagnosed by myofilaments, attachment plaques, plasmalemmal caveolae, and lamina; GIST by processes or cell bodies full of intermediate filaments, solitary focal densities amid intermediate filaments, attachment plaques with incomplete lamina, scarce myofilaments, and smooth endoplasmic reticulum; GANTs by neuroendocrine granules, cell bodies/processes full of intermediate filaments (more rarely microtubules), and smooth endoplasmic reticulum; fibroblastic/myofibroblastic tumors by abundant rough endoplasmic reticulum, myofilaments, and fibronexuses. Seventy-three tumors (89%) were successfully subclassified, as 5 leiomyoma/leiomyosarcoma (6%), 36 GISTs (44%), 22 GANTs (27%), 10 fibroblastic and myofibroblastic tumors (12%). Results indicated overlap between poorly differentiated leiomyosarcoma and GIST, and between GIST and GANT. GANT is emphasized as a neuronal tumor identifiable by electron microscopy, and thereby distinguishable from GIST. [ABSTRACT FROM AUTHOR]

Describes the monotypic angiomyolipoma (AML) of the nasal cavity. Association of AML with tuberous sclerosis; Components of AML; Ulceration of the epithelium covering the tumor.

Some interpretational problems associated with the myofibroblast, which affect how this cell is identified, are discussed. Questions addressed include distinguishing between "external" lamina ("basement membrane") and the fibronectin fibril of the fibronexus; the nature of stress fibers (bundles of smooth-muscle myofilaments with focal densities); the utility of some of these features to distinguish between myofibroblastic and smooth-muscle cell surfaces; and cytoskeletal immunophenotype. The following points are emphasized. Myofibroblasts have a surface characterized by prominent fibronectin fibrils and fibronexus junctions, which are distinct from lamina ("basement membrane"). This can permit a distinction to be made between smooth-muscle and myofibroblastic lesions and tumors. Myofibroblasts are typically positive for vimentin and α-smooth-muscle actin, but desmin is not a useful discriminant between smooth-muscle and myofibroblastic lesions. The main features for defining the myofibroblast are abundant rough endoplasmic reticulum; modestly developed peripheral myofilaments with focal densities (stressfibers); fibronexus junctions; vimentin and smooth-muscle actin immunostaining. Other features include a Golgi apparatus and collagen secretion granules, gap junctions, and actin-associated nondesmosomal junctions. Illustrations of the usefulness of these criteria in the diagnosis of soft-tissue lesions (myofibrosarcoma, so-called myofibroblastoma) are given. [ABSTRACT FROM AUTHOR]

Examines the effect of smooth-muscle actin expression or the presence of myofilaments on tumoral cells and cells of widely different histogenetic type. Examples of smooth-muscle type myofilaments occurring in nonmuscle cells; Implications of the transdifferentiation toward smooth muscle cells on tumor diagnosis and on understanding cell biological mechanisms involved in disease.

The endoplasmic reticulum (ER) is the largest membranous network serving as a region for protein, lipid and steroid synthesis, transport and storage. Detailed information about ER-cisternae, ER-tubules and rough endoplasmic reticulum (rER) is scarce in human blood cells. This study describes a series of giant inclusions and Auer bodies in promyeloblasts in six patients with acute promyelocytic leukemia (APL), by light microscopy, transmission electron microscopy (TEM) and cytochemical stains. TEM revealed that giant inclusions and pro-Auer bodies were associated with rER and surrounded by tubular structures composed of degenerated or redundant membrane in promyeloblasts, which corresponded with elements of the ER system. This paper reveals that in the promyeloblasts of APL, ER is the source of and transforms progressively into giant inclusions and Auer bodies. [ABSTRACT FROM AUTHOR]

Examines the identification of amorphous matrices by electron microscopy. Implications for the control of cell biological processes; Use of immunohistochemistry for the presence of proteins; Capability of laminin to promote tumor cell migration.

The monocytes in acute monocytic leukemia (AML-M5b) were analyzed by scanning and transmission electron microscopy (SEM and TEM) to understand more fully their structure and origin. By SEM, monocytes exhibited localized expansions of the surface, some of which appeared to bud off as surface vesicles (SVs). Filopodial processes and pseudopodia were also present. TEM demonstrated that the SVs were composed of a double-membrane at the pole away from the cell body, and a single membrane nearer to the cell body. In the peripheral cytoplasm, intracellular vesicles (IVs) had the appearance of vacuoles and were enclosed by single membranes. Most SVs were characterized by a notch as a rER edge and an expanded head. Filopodial processes had the same thickness of 40 nm as the SV walls, which suggested a close developmental relationship between the two. Pseudopodia between SVs were irregular in size. Rod-like rER cisternae were prominent in the peripheral cytoplasm and some showed a close physical juxtaposition as to suggest a transition from rER to IVs to SVs. Ultrastructural cytochemistry demonstrated activity of 5'-nucleotidase over rER, SVs, filopodial processes and pseudopodia, and a patchy reaction over other areas of plasma membrane. Overall, the results indicated that rER transforms into SVs, filopodial processes and pseudopodia, as a way of integrating cytoplasmic membranes into the plasma membrane. [ABSTRACT FROM AUTHOR]

Presents a letter to the editor in response to the article "Epitheloid Leiomyosarcoma of the External Deep Soft Tissue," by T. Yamamoto, R. Minami, C. Ohbayashi and M. Inaba, published in a 2002 issue of the journal "Archives of Pathology and Laboratory Medicine."

Fascia lata is an important element of the fascial system, which forms the continuum of connective tissue throughout the body. This deep fascia envelops the entire thigh and hip area and its main function is to transmit mechanical forces generated by the musculoskeletal system of the lower extremities. Fascia lata is also known as a useful and easily harvested graft material. Despite its crucial role in lower extremity biomechanics and wide-ranging applications in plastic and reconstructive surgery, both the structure of fascia lata and particularly the cells populating this tissue are relatively unexplored and therefore poorly understood. The aim of this study was to characterize the main cell populations encountered within human fascia lata and to try to understand their role in health and diseases. Pathologically unchanged human fascia lata was obtained post mortem from adult males. The specimens were analyzed under light, electron, and confocal microscopy. On the basis of different visualization techniques, we were able to characterize in detail the cells populating human fascia lata. The main cells found were fibroblasts, fibrocytes, mast cells, cells showing myoid differentiation, nerve cells, and most interestingly, telocytes. Our results supplement the formerly inadequate information in the literature regarding the cellular components of deep fascial structure, may contribute to a better understanding of the pathogenesis of fascial disorders and improve fascia lata application as a graft material. [ABSTRACT FROM PUBLISHER]

Presents a letter to the editor about squamous cell carcinoma.

The 2 micrographs in this case illustrate single-membraned bodies associated with clear cytoplasmic spaces, the author suggests that they might be lysosomes or peroxisomes. These are the most likely candidates, although absolutely unambiguous features indicating one or the other are lacking, as are supportive data from other techniques. If they are lysosomes, they do not have the fine space of uniform width just beneath the limiting membrane, often seen in well-preserved lysosomes. If they are peroxisomes, they lack crystalloids. Given that this is a surgical specimen, the opportunities for specialized techniques for example, hydrolase or catalase electron-histochemistry to clarify the nature of these somewhat limited.

To identify the nature of foam cells in atherosclerosis, carotid atherosclerotic plaques (CAPs) from six patients were studied. Hematoxylin-and-eosin, Congo Red and Oil Red O staining were used to study histopathologic alterations in CAPs. CD31, α-smooth-muscle actin (α-SMA), CD68, desmin and S100 were stained immunohistochemically. The ultrastructure of foam cells was analyzed by transmission electron microscopy (TEM). CAPs were shown to be composed of a fibrous cap covering a dome-shaped mass with a peripheral, circumferential fringe merging with a basal band which itself met the tunica media, the latter consisting of smooth-muscle cells (SMCs). The interior of the dome-shaped mass exhibited fibrosis, neovascularization, hemorrhage, necrosis and calcification. Lipid droplets identified by histological stains and TEM were found in the rounded epithelioid foam cells regarded as macrophages, as well as in spindled cells interpreted here as lipoleiomyocytes (lipid-containing SMCs), lipofibroblasts and lipomyofibroblasts; and all these cells were located in different regions of the CAPs. All of these lipid-laden cells were strongly positive for CD68 but negative for desmin. Foam cells were weakly positive for α-SMA, CD31 and S100. The results indicate that the light microscopically identifiable population of foam/lipid-laden cells hide a spectrum of diverse differentiation ranging from the expected macrophage phenotype to non-macrophage phenotypes. The origin of these diverse cell phenotypes in terms of multipotential mesenchymal precursors and the origin of the intracellular lipid are discussed. [ABSTRACT FROM AUTHOR]

The aim of this study is to report the clinicopathologic characteristics of 3 cases of alveolar rhabdomyosarcoma with neuroendocrine/neuronal differentiation. Specimens of 3 cases of alveolar rhabdomyosarcoma were studied using histologic, immunohistochemical, ultrastructural, and molecular genetic techniques. The patients were a 19-year-old man with metastatic alveolar rhabdomyosarcoma in a groin lymph node, a 16-year-old girl with alveolar rhabdomyosarcoma of the perineum, and a 20-year-old man with recurrent orbital alveolar rhabdomyosarcoma. Microscopically, case 1 was composed of compact sheets of medium to large tumor cells. Cases 2 and 3 were small blue round cell tumors. Cases 1 and 3 were solid throughout, whereas case 2 demonstrated alveolar and solid architecture. By immunohistochemistry, the following markers were positive: desmin (3/3), myogenin (3/3), synaptophysin (3/3), and chromogranin (2/3). Ultrastructurally, sarcomeric filaments were seen in all cases, while neuroendocrine granules were detected only in case 1. PAX:FKHR fusion transcript was identified in case 2, case 3 had a variant PAX3 transcript, and case 1 was negative. The data presented expands the known differentiation of alveolar rhabdomyosarcoma. [ABSTRACT FROM AUTHOR]

A case of multiple myeloma is reported in which the bone marrow contained sheets of histiocytes with light microscopic features mimicking Gaucher cells. The patient had no clinical evidence of inherited Gaucher's disease. These pseudo-Gaucher cells obscured neoplastic plasma cells causing diagnostic difficulty. [ABSTRACT FROM AUTHOR]

Two cases of malignant melanoma are reported in adults exhibiting rhabdomyoblastic differentiation to alert pathologists to this rare variant of malignant melanoma. One of the cases presented as a metastasis in a submandibular lymph node, and the other was a primary skin melanoma. There are only a few published reports on melanocytic tumors with rhabdomyoblastic differentiation, mainly occurring in giant congenital nevi. Both cases reported here were confirmed by immunohistochemistry. Both cases were also studied by electron microscopy, and one showed distinctive ultrastructural features of striated muscle. [ABSTRACT FROM AUTHOR]

The article reports on the structural characterization of myofibroblasts in the bladder by researchers from Manchester, England. The cellular physiology of the lower urinary tract is in an exciting phase thanks to the identification of a novel cell type, present in the bladder within the detrusor and in the suburothelial space. Such cells might have the potential to intercede in several fundamental processes, including processing of sensory information, pacemaking, and modulating contractile function.

To clarify the characteristics and origin of the cellular components in atherosclerosis, carotid atherosclerotic plaques (CAPs) of four patients were studied by light microscopy using hematoxylin-eosin, Congo red and alpha-smooth-muscle actin stains, and by transmission electron microscopy of different regions of CAPs. By light microscopy, CAPs were composed of 1) a fibrous cap; 2) an atherosclerotic core presenting focal fibrosis, neovascularization, hemorrhage, necrosis, chondrification and ossification; and 3) a basal band composed of a hyperplasic pseudo-media and affected tunica media. Ultrastructurally, the CAPs contained a diversity of cells including fibroblasts, myofibroblasts, osteochondrocytes, vascular smooth-muscle cells, foam cells and other myoid cells characterized by varied features of the above mentioned cells. The results indicated that CAPs were derived from a proliferation of multipotential mesenchymal stem cells, leading to the presence of degenerated foam cells and lipid-laden cells. [ABSTRACT FROM AUTHOR]

Megakaryocytes engage in the synthesis of a variety of molecular and macromolecular constituents to build-up characteristic megakaryocyte structure and form proplatelets in a series of cells from megakaryocyte precursors to the fully matured cell. The process is illustrated in this review by light microscope morphology and transmission electron microscopy, which emphasizes new findings in human in vivo megakaryocytes, thereby making a contrast with the abundant literature on megakaryocytes from experimental animal and human in vitro material. Four stages are identified and described, based on the development of characteristic structures including α-granules, dense granules (dense-core granules), the demarcation membrane system (DMS), and proplatelets. The mechanism of DMS development is discussed, in terms of hypotheses suggesting origin from the plasma membrane, and contributions of membrane from the Golgi apparatus and endoplasmic reticulum. The formation of the marginal zone is also discussed, which is suggested to result from a circumscription of the peripheral organelle-free cytoplasmic fringe by peripheral circular cytoskeletal elements such as cytoplasmic actin and microtubules. [ABSTRACT FROM AUTHOR]

Object: To study the relationship between monocyte/histiocyte activation and myelodysplastic syndrome (MDS). Methods: Analyzing ultrastructure and myeloperoxidase reaction of nucleated cells in bone marrow from 59 cases of MDS by transmission electron microscopy. Four groups of MDS were subdivided on the basis of their content of activated inflammatory cells - morbid hematopoiesis with minimal inflammatory cell activation (MH-MICA); MDS with monocytic system activation (MSA); MDS with lymphocyte activation (LCA); and MDS with granulocyte activation (GCA). Results: About 20, 22, 7, and 10 cases were classified as MH-MICA (34%), MSA (37%), LCA (12%), and GCA sub-types (17%), respectively. About 3, 5, 0, and 3 cases from MH-MICA, MSA, LCA, and GCA, respectively, underwent leukemic transformation within 2 years. Conclusion: The findings suggest that activation of inflammatory cells in bone marrow is an important feature of MDS, and that monocytes/histocytes are perhaps the most prominent cellular participants in the pathogenesis of MDS. [ABSTRACT FROM AUTHOR]

Congenital dyserythropoietic anemias (CDAs) are a group of hereditary disorders characterized by ineffective erythropoiesis and distinct morphological abnormalities of erythroblasts in the bone marrow. Most cases of CDA, caused by a wide spectrum of mutations, have been reported from Europe and Mediterranean countries, while a few cases have been described in China. Here, we present three cases of CDA, one from one family and two from a second unrelated family, with typical morphologic features and clinical presentations. Sequence analysis of CDA-related genes revealed that the proband with CDA Ι in the first family was a compound heterozygote of CDAN1 with mutation IVS-12+2T>C and c. 3389C>T, while both probands with CDA ΙΙ in the second family were a homozygote of the SEC23B gene with mutation c.938G>A (R313H). This study suggests that more patients with CDA, sharing a phenotype and genetic background like those of European and Mediterranean origin, remain to be diagnosed and reported in China. [ABSTRACT FROM AUTHOR]

Objective: To describe characteristics of monocytes and histiocytes in the bone marrow of patients with a confirmed and suspected diagnosis of reactive histiocytosis. Methods: 14 patients with a confident diagnosis of reactive histiocytosis or with a suspected diagnosis were inpatients at the Tianjin Blood Diseases Hospital between 2008 and 2012. Nucleated cells from bone marrow were observed by light microscopy - morphologically and immunohistochemically for histiocyte antigens - and ultrastructurally by transmission electron microscopy. Results: Monocytes, atypical histiocytes, macrophages, hemophagocytes, reticular cells and dendritic cells were significantly increased in 9, 9, 5, 3, 3 and 2, respectively, of the 14 cases. Atypical histiocytes expressed some morphological characteristics of promonocytes. Conclusion: Monocytes, atypical histiocytes, macrophages, hemophagocytes, reticular cells and dendritic cells were increased in different relative degrees in patients with bone marrow reactive histiocytosis or suspected reactive histiocytosis. The increase in numbers of monocytes, atypical histiocytes and macrophages was a particularly significant feature. It is argued that atypical histiocytes with immature monocyte features might be precursors of hemophagocytes, reticular cells or dendritic cells. [ABSTRACT FROM AUTHOR]

Clear-cell sarcoma (CCS) is a soft-tissue neoplasm that morphologically resembles cutaneous malignant melanoma but has a distinct molecular profile. Gastrointestinal and intra-abdominal CCSs are very rare. Here, the authors present 3 cases of intra-abdominal CCS and review the literature. Of these cases, 2 involved the small bowel, and 1 involved the peritoneum. Cases 1 and 3 had the characteristic CCS morphology, but case 2 was morphologically unusual and therefore difficult to diagnose. It had relatively small cells with less prominence of clear cells; many pseudoglandular structures were also present. It also showed aberrant expression of epithelial membrane antigen (EMA). The other 2 cases also involved some diagnostic uncertainty and were therefore referred to specialized centers. The authors wish to emphasize the importance of molecular studies in making a conclusive diagnosis of intra-abdominal CCS. [ABSTRACT FROM AUTHOR]

Amorphous matrices related with basement membrane have been described before, in peri-vascular locations in malignancies, reactive lesions and normal cerebral cortex and on the surfaces of benign tumoral fibroblasts. They appear to be compartments comprising the proteins normally found in an organised (laminate) lamina (lamina densa/lamina lucida), but not in fact organised in that manner, and have a disorganized a amorphous appearance. By light microscopy immunohistochemistry, BM of vessels and epithelial cells stained positively for laminin and collagen IV, two of the main proteins characterizing a conventional basal lamina. This paper discusses the possibility that ultrastructural findings in correlation with those of immunohistochemistry supply more information for the biological behavior of breast cancer that seems to be influenced by the pattern of organization of BM proteins. These models of organization may be involved in the metastatic process. [ABSTRACT FROM AUTHOR]

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare aggressive lymphoma derived from plasmacytoid dendritic cells or precursor dendritic cells. Despite some 240 reported cases, its morphology and especially ultrastructure has not been satisfactorily studied. A case is reported of a 13 year old boy, who, despite chemotherapy, died within a 12-month period. The electron microscopy findings - microvillous processes, nuclei with slight irregularities, a moderate amount of heterochromatin, and rough endoplasmic reticulum in the form of long, narrow profiles, often in parallel arrangements - taken together, serve to distinguish BPDCN from other neoplastic cells, such as monocytes, plasma cells and the cells of chronic lymphocyte leukemia. [ABSTRACT FROM AUTHOR]