A group of sclerosing epithelioid fibrosarcomas with low-level amplified EWSR1-CREB3L1 fusion gene in children.

Sclerosing epithelioid fibrosarcoma (SEF), typically arising in middle-aged and older adults, is a rare malignant fibroblastic neoplasm characterized by epithelioid fibroblasts embedded in sclerotic hyalinized stroma. This tumor frequently harbors translocation between EWSR1 and CREB3 subfamily members. Here, we describe four cases of SEF with unique genetic characteristics in children. All tumors were located in the deep soft tissue of the trunk and celom. Histopathologically, the tumors were featured by prominent hyalinized sclerotic collagenous stroma within which relatively bland and monomorphic epithelioid cells were arranged in cords, nests, or sheets. Low-grade fibromyxoid sarcoma-like zones varied among cases. MUC4 was strong and diffuse. CD99 was positive. Transmission electron microscopy demonstrated spindle or polyhedral neoplastic cells with a collagen fiber-rich stroma. Interphase fluorescence in situ hybridization (FISH) revealed local amplification of the EWSR1 locus. Whole-genome sequencing indicated translocation between EWSR1 and CREB3L1 together with low-level amplification of the fusion parts. RT-PCR and Sanger sequencing confirmed the fusion transcript. Single nucleotide polymorphism and FISH analyses demonstrated co-deletion of 11p and 22q. The consistent genetic features indicated the presence of a unique molecular variant of SEF. DATA AVAILABILITY STATEMENT: The data used to support the findings of this study are available from the corresponding author upon request.

Line-field confocal optical coherence tomography of xanthogranuloma: Correlation with vertical and horizontal histopathology.

Line-field confocal optical coherence tomography (LC-OCT) is a new noninvasive technique for a real-time, vertical, and horizontal imaging of the skin at cellular resolution. A 47-year-old female presented with a 6-month history of an asymptomatic yellowish papule. LC-OCT evaluation was able to show the diagnostic microscopic features of xanthogranuloma and showed an excellent correlation with vertical and horizontal histopathological sections by revealing enlarged dermal papillae containing multiple, bright roundish giant cells, corresponding to foamy histiocytes, and giant cells characterized by a dark center surrounded by a highly hyper-refractile peripheral ring, corresponding to Touton cells. LC-OCT may represent a valid, noninvasive alternative to histopathological examination in clinically atypical cases of xanthogranuloma.

Soft tissue myoepithelial carcinoma-a case report with molecular and electron microscopic analysis.

Myoepithelial tumors are rare neoplasms that primarily occur in the salivary gland but over the last decade have also been described in other locations, including soft tissue. Myoepithelial carcinoma of soft tissue has shown to have a recurrence rate of 39-42% and distant metastases in 32-53% of patients. The only known predictor of malignancy in soft tissue myoepithelial tumors described is cytologic atypia. There are no other validated criteria for differentiating benign and malignant tumors, neither for grading nor for standard of care for these tumor types. Herein, we present a case of myoepithelial carcinoma of inguinal soft tissue in a 37-year male. We also describe the molecular and previously sparingly described detailed electron microscopic features of this case.

Ultrastructure of CIC-DUX4 sarcoma: the first pathological report.

CIC-DUX4 sarcoma (CDS) is a recently identified subtype of small round cell sarcoma. Morphologically, CDS partially resembles Ewing sarcoma (ES) and has been classified as "ES-like sarcoma"; however, detailed clinicopathologic and molecular genetic analyses have indicated that CDS is a new independent disease. Many studies have provided light microscopic, immunohistochemical, and genetic information about CDS. However, ultrastructural findings associated with this sarcoma are lacking. The aim of this study was to investigate the ultrastructure of CDS tumors and to compare their features with those of ES. We examined two cytogenetically confirmed CDS cases. We found that, compared to typical ES, CDS presented heterogeneity: in cell density, from tightly packed to loosely unconnected areas; in cell shape, from polygonal to pleomorphic with small processes; and in nuclear shape including round, oval, polygonal, elongated, invaginated, or wrinkled formations. However, abundant glycogen in the cytoplasm and rare cell adhesion apparatus between cells are major similarities between CDS and typical ES. Neuroendocrine granules, which are seen in rare ES cases, could not be identified in these two CDS cases. Although cytogenetic differences can validate a definite diagnosis, ultrastructural features could also provide important information about the differences between CDS and ES.

Multiple calcifying fibrous pseudotumors of the pleura: ultrastructural analysis provides insight on mechanism of dissemination.

Calcifying fibrous pseudotumor (CFP) is a rare, benign soft tissue tumor that may uncommonly arise in the pleura. These tumors can show multifocal dissemination across the pleural surface, but the mechanism underlying this dissemination is unclear. Review of previously reported cases of pleural CFP demonstrates a strong predilection for basal and diaphragmatic pleural surfaces, and a significantly higher rate of multifocality compared with other locations. We present a 59-year-old male with multiple CFP of the pleura. Reactive-appearing adhesions spanning the pleural surfaces were present, and by electron microscopy, were involved by tumor. We suggest this is the likely mode of dissemination across the pleural surfaces.

Malignant granular cell tumors: the role of electron microscopy in the definitive diagnosis of an extremely aggressive soft tissue neoplasm.

Granular cell tumors (GCTs) are rare soft tissue neoplasms which may be multicentric. The vast majority are benign, however approximately 100 malignant GCTs have been reported, with only 8 originating in the vulva. Malignant GCTs are very aggressive with very poor survival rates. As the diagnosis of malignant GCT carries an extremely poor prognosis, the utilization of EM ensures that the most accurate diagnosis possible can be rendered.

Fibroma-like PEComa: A Tuberous Sclerosis Complex-related Lesion.

Perivascular epithelioid cell tumor (PEComa), mesenchymal tumors morphologically characterized by epithelioid cells, coexpress melanocytic and muscle markers. Herein, we describe a heretofore-undescribed tuberous sclerosis complex (TSC)-related neoplasm, morphologically resembling a soft tissue fibroma-like lesion, but showing an immunophenotype resembling PEComa. We identified 3 soft tissue fibroma-like lesions in individuals with TSC. We also evaluated 6 TSC-related periungual fibroma as well as a range of non-TSC fibroma-like lesions (n=19). Immunohistochemistry for HMB-45, desmin, smooth muscle actin, TFE3, and S100 was performed on the TSC-related fibromas. Periungual fibromas and non-TSC fibroma-like lesions were also stained for HMB-45. All 3 TSC patients were female, ranging in age from 4 to 51 years (mean, 26.7 y). Two tumors were located in extremities and 1 on the chest wall. The tumors showed elongated to stellate spindle-shape cells, prominent collagenous background, and lacked mitotic activity and cytologic atypia. Immunohistochemically, all 3 tumors were positive for HMB-45; smooth muscle actin or desmin was positive in both tumors tested. TFE3 was negative. All patients were alive with no evidence of disease with median follow-up of 55 months (range, 6 to 131 mo). Non-TSC fibroma-like lesions and oral and periungual fibromas were negative for HMB-45. Fibroma-like PEComa, a newly recognized soft tissue tumor with a strong association with TSC, mimics soft tissue fibroma but shows reactivity with melanocytic markers.

Elastofibroma dorsi: a case report with an immunohistochemical and ultrastructural studies.

Elastofibroma is a rare, benign, fibrous tumor formed by the proliferation of characteristic elastic fibers that commonly occurs between the lower margin of the scapula and the ribcage. We undertook a histochemical, immunohistochemical, and ultrastructural study of an elastofibroma dorsi beneath the right scapula of a 77-year-old woman. Tumor cells comprised collagen fiber bundles, numerous elastic fibers, and spindle cells resembling fibroblasts. The elastic and collagen fibers in the tumor were stained positively with Elastic van Gieson and Masson trichrome staining, respectively. Immunostaining showed that the fibroblasts were strongly positive for CD34, positive for vimentin, and weakly positive for α-smooth muscle actin. Ultrastructural observations revealed elastin and microfibrils between numerous irregularly arranged collagen fiber bundles. Signs suggestive of elastin deposition were also evident in the tangled collagen fibers themselves. The fibroblasts contained a large amount of rough endoplasmic reticulum and were surrounded on the outside of cells by microfibrils and collagen fibers. Although fibroblasts may produce large quantities of elastin, microfibrils, and collagen, our findings suggested that the deposition of elastin on collagen fibers may be involved in the formation of abnormal elastic fibers.

La elastografía: una nueva aplicación de la ecografía. ¿Cuál es su utilidad clínica? / The clinical utility of elastography, a new ultrasound technique

La elastosonografía es el resultado de la conjunción entre la elastografía y la ecografía en modo-B, donde se muestran, en tiempo real, los parámetros relativos a la organización estructural de los tejidos. De esta manera, vemos reflejadas, en una técnica no invasiva, las características mecánicas de cada tejido. Las diferentes técnicas de elastografía (cualitativas y cuantitativas en ultrasonido o resonancia magnética) se basan en la hipótesis de que los tejidos blandos se deforman más que los rígidos y que estas diferencias pueden ser plasmadas en imágenes. La elastografía aporta una nueva perspectiva a la ecografía convencional: la rigidez de los tejidos que junto con la información anatómica del modo-B y la vascular del modo-Doppler proporciona una información clave para el diagnóstico. En este artículo se pretende realizar un pequeño resumen de lo que es la elastografía, los tipos que existen, y el abanico de posibilidades que nos ofrece (AU)

Sonoelastography combines elastography and B mode ultrasonography to show parameters related to the structural organization of tissues in real time. Thus, this noninvasive technique shows us the mechanical characteristics of each tissue. The different elastography techniques (qualitative and quantitative, in ultrasonography or magnetic resonance imaging) are based on the hypothesis that soft tissues are more deformable than stiff tissues and that these differences can be captured in images. Elastography adds a new perspective to conventional ultrasonography: it reflects the stiffness of the tissues, and this information, together with the anatomic information from B mode imaging and the vascular information from Doppler, is key for the diagnosis. This article aims to provide a brief summary of what elastography is, the different types of elastography, and the range of possible applications of this technique (AU)

[Significance of sonographically guided percutaneous needle biopsy in the diagnostics of soft tissue tumors]. / Stellenwert der sonographisch kontrollierten perkutanen Stanzbiopsie in der Diagnostik von Weichgewebstumoren.

BACKGROUND: The role of percutaneous needle biopsy in the diagnostics of soft tissue tumors is controversially discussed. The specificity of this method has been examined in this study based on the collective of patients treated in our university hospital. Secondly, the influence of the specialization of the treating surgeon has been evaluated. PATIENTS AND METHODS: This study included 96 patients who underwent percutaneous needle biopsy and, if necessary, surgical resection. The specificity, logistic requirements and possible complications of percutaneous biopsy were evaluated. Special attention was paid to the influence of specialization of the treating surgical team on the specificity of the method. RESULTS: The results of the biopsy were able to define the entity of the lesion correctly in 69.7 %, the dignity in 75.0 % and the grading in 72.0 % of the cases. In the group treated by a specialized team, the specificity of the method was 84.6 % concerning the entity of the lesion, 84.6 % concerning the dignity and 80 % concerning the grading. With regard to the entity the specificity was significantly increased (p < 0.05). CONCLUSION: The findings show that percutaneous needle biopsy represents a logistically simple and efficient diagnostic method for soft tissue tumors which is rarely associated with complications. Subsequent treatment should be performed in a specialized centre.

Pulsed focused ultrasound exposures enhance locally administered gene therapy in a murine solid tumor model.

Gene therapy by intratumoral injection is a promising approach for treating solid tumors. However, this approach has limited success due to insufficient distribution of gene vectors used for gene delivery. Previous studies have shown that pulsed-focused ultrasound (pFUS) can enhance both systemic and local delivery of therapeutic agents in solid tumors and other disease models. Here, murine squamous cell carcinoma flank tumors were treated with single intratumoral injection of naked tumor necrosis factor-alpha (TNF-α) plasmid, either with or without a preceding pFUS exposure. The exposures were given at 1 MHz, at a spatial average, temporal peak intensity of 2660 W cm(-2), using 50 ms pulses, given at a pulse repetition frequency of 1 Hz. One hundred pulses were given at individual raster points, spaced evenly over the projected surface of the tumor at a distance of 2 mm. Exposures alone had no effect on tumor growth. Significant growth inhibition was observed with injection of TNF-α plasmid, and tumor growth was further inhibited with pFUS. Improved results with pFUS correlated with larger necrotic regions in histological sections and improved distribution and penetration of fluorescent surrogate nanoparticles. Electron microscopy demonstrated enlarged gaps between cells in exposed tissue, and remote acoustic palpation showed decreases in tissue stiffness after pFUS. Combined, these results suggest pFUS effects may be reducing barriers for tissue transport and additionally lowering interstitial fluid pressure to further improve delivery and distribution of injected plasmid for greater therapeutic effects. This suggests that pFUS could potentially be beneficial for improving local gene therapy treatment of human malignancies.

The contribution of electron microscopy to the characterization of soft tissue fibrosarcomas.

In recent years, with the application of immunohistochemical and cytogenetic methods, numerous lesions formerly diagnosed as fibrosarcoma were reclassified as other malignant soft tissue tumors, and therefore conventional fibrosarcoma has largely become a diagnosis of exclusion. On the other hand, several new entities belonging to the group of fibrosarcomas have been characterized, including low-grade fibromyxoid sarcoma / hyalinizing spindle cell tumor with giant rosettes, sclerosing epithelioid fibrosarcoma, acral myxoinflammatory fibroblastic sarcoma, and the epithelioid variant of myxofibrosarcoma. Electron microscopy has contributed to the identification of the fibroblastic phenotype in these fibrosarcoma variants and still retains a central role in the differential diagnosis of these soft tissue sarcomas, thus helping to render specific diagnoses and to broaden the spectrum of fibrosarcoma variants.

Inhibin-α and synaptophysin immunoreactivity in synovial sarcoma with granular cell features.

We recognized immunoreactivity for the α subset of inhibin and synaptophysin in synovial sarcomas with granular cell features. Histologic findings of 90 cases of synovial sarcoma were reviewed. Two (2.2%) of the 90 cases had granular cell features, showing sheet or nested proliferation of characteristic epithelioid cells with abundant eosinophilic and granular cytoplasm, in addition to the typical spindle cell component. The 2 cases were both female (aged 86 and 76 years). The tumors were located in the foot and the retroperitoneum and measured 3.5 and 14 cm in maximum diameter. Reverse transcriptase polymerase chain reaction analysis revealed SS18-SSX1 transcripts in both cases. SS18 gene rearrangement was detected in granular cells as well as spindle cells by chromogenic in situ hybridization. Immunohistochemistry found the granular cells to be positive for inhibin-α in both cases and for synaptophysin in 1 case, whereas spindle cells were not. Thirty-six cases (20 monophasic fibrous, 11 biphasic, and 5 poorly differentiated synovial sarcomas) were additionally examined for comparison; they showed no immunoreactivity for inhibin-α or synaptophysin. This is the first report of immunoreactivity for inhibin-α and synaptophysin in synovial sarcoma. These immunohistochemical findings might be characteristic of synovial sarcomas with granular cell features.

Multicentric fibromyxoid peripheral nerve sheath tumor (multicentric schwannoma) in a dromedary camel (Camelus dromedarius): morphopathological, immunohistochemical, and electron microscopic studies.

During postslaughter inspection of a 4-year-old male dromedary camel (Camelus dromedarius), numerous small nodules to large masses up to 4 cm in diameter were found on the serosal surfaces of forestomachs, large intestines, mesentery, liver, and spleen. Grossly, the masses were discrete, round, smooth, and white to gray that bulged from the serosal layer. Cut surfaces of the masses were discrete, round, white, and relatively homogeneous without any necrotic foci. Histopathologically, the masses were encapsulated and composed of a mixture of round and spindle-shaped cells in loose whorls of neoplastic cells with small elongated hyperchromatic wavy nuclei and a small amount of pale eosinophilic, poorly defined cytoplasm. Masson's trichrome staining showed mild amounts of collagen fibers forming an irregular, loose stroma. In immunohistochemistry, immunoreactivity for the Schwann cell marker (S100) was diffusely positive in the neoplastic cells. The immunoreactivity for CK, c-kit, and CD34 were negative. Ultrastructural examination confirmed the tumor was entirely formed of neoplastic Schwann cells. On the basis of the histopathological, immunohistochemical, and ultrastructural findings, the tumors were diagnosed as multicentric fibromyxoid peripheral nerve sheath tumor (multicentric schwannoma). This tumor has not been previously recorded in camel worldwide.

[Extracranial meningioma: morphological and histogenetical aspects and relations with perineurioma].

The clinicomorphological, immunohistochemical, and ultrastructural characteristics of 11 cases of extracranial meningioma versus 79 soft tissue perineuriomas were studied. There were significant similarities (cell morphology, immunoprofile, ultrastructural features of perineurial differentiation) of both entities. Considering the point of view that arachnoid and perineurial cells are anatomically, embryologically, and functionally related, it is most possible that extracranial meningiomas may be derived from perineurial cells (or their progenitor cell) rather than from displaced arachnoid cells.

An atypical peripheral nerve sheath tumour with pseudoglandular architecture in a dog.

This case describes a subcutaneous soft tissue tumour in a German Shepherd dog. Histologically, the lesion was characterized by proliferating ovoid cells, loosely arranged in a collagenous to myxoid stroma, and by numerous pseudoglandular structures lined by neoplastic cells. Immunohistochemically, neoplastic cells were labelled with vimentin, glial fibrillary acidic protein and S100 antibodies, but not with cytokeratin, desmin and smooth muscle actin antibodies. Ultrastructurally, neoplastic cells were characterized by numerous mitochondria surrounded by endoplasmic reticulum and contained few secondary lysosomes. This tumour was diagnosed as a subcutaneous peripheral nerve sheath tumour (PNST) with pseudoglandular architecture. This case illustrates the morphological diversity of PNST and provides new insight into the differential diagnosis of cutaneous tumours of similar morphology in the dog.

IGF2 is highly expressed in pediatric undifferentiated sarcomas and reveals two distinct cytoplasmic trafficking patterns.

Pediatric undifferentiated soft tissue sarcomas (USTSs) are tumors composed of primitive mesenchymal cells. As such, they form an attractive model for studying the early events in sarcoma development. In an effort to better understand the critical molecular aberrations leading to sarcoma development, gene expression array analysis and post-array validation techniques were applied to several USTSs; the results were consistent with upregulation of the excitatory components of the insulin-like growth factor (IGF) pathway. Particularly high expression of the insulin-like growth factor 2 (IGF2) ligand was seen and confirmed by real-time reverse transcriptase-polymerase chain reaction. Immunohistochemistry performed using antibodies against IGF2 revealed overexpression of the IGF2 protein in 19 of 21 (90%) USTSs and revealed 2 distinct staining patterns, 1 in which there was diffuse cytoplasmic staining (16/19) and 1 in which there was punctate perinuclear positivity (3/19). Using ultrastructural immunogold localization of IGF2, it was determined that IGF2 was primarily localized to Golgi-derived vesicles and multivesicular bodies in tumor cells showing the punctate pattern, and to both the cytoplasm and plasma membrane of tumor cells showing the diffuse pattern. The results suggest that upregulation of the IGF pathway in pediatric USTSs is a critical early event in the development of sarcomas. Furthermore, findings from the immunocytochemical and immunogold analyses confirm the presence of 2 different cytoplasmic trafficking patterns and storage motifs of IGF2 within this type of tumor. Given that in one subcellular pattern the IGF2 protein does not appear to reach the membrane, these findings may have functional significance.