L‐type amino acid transporter‐1 and CD98 expression in bone and soft tissue tumors

L‐type amino acid transporter‐1 (LAT1) is expressed in many cancers. We examined LAT1 and CD98 expression immunohistochemically in surgically resected specimens of various bone and soft tissue tumors. Out of 226 cases, 79 (35%) were LAT1⁺ and 95 (42%) were CD98⁺. In bone tumors, LAT1 was highly expressed in osteoblastoma (89%), chondrosarcoma (50%), and osteosarcoma (60%); in soft tissue tumors, LAT1 was highly expressed in rhabdomyosarcoma (80%), synovial sarcoma (63%), Ewing's sarcoma (60%), epithelioid sarcoma (100%) and angiosarcoma (100%). In malignant soft tissue tumors, LAT1 expression was associated with higher histological grade. High CD98 expression was seen in many bone tumors of intermediate and high malignancy. Among soft tissue tumors, CD98 was expressed in tendon sheath giant cell tumor and malignant peripheral nerve sheath tumor (57%), Ewing's sarcoma (50%) and undifferentiated sarcoma (64%). Some of the malignant soft tissue tumors expressed both LAT1 and CD98. This study showed that LAT1 and CD98 was expressed in many malignant and intermediate bone tumors, and some malignant soft tissue tumors.     

Mesenchymal neoplasms: Is it time for cytology? New perspectives for the pre-operative diagnosis of soft tissue tumors in the molecular era

Soft tissue tumors comprise a great variety of common and rare entities with overlapping features. Their diagnosis is based on the evaluation of several histological parameters which are difficult to assess on small incisional biopsies. Useful diagnostic markers in the field of soft tissue tumors include: 1) molecular biomarkers detecting pathogenetically relevant, distinctive alterations; 2) immunohistochemical surrogate biomarkers of pathogenetically relevant, distinctive molecular alterations; 3) highly specific immunohistochemical biomarkers indicating tumor differentiation. Their introduction in clinical practice has revolutionized the pre-operative diagnosis of soft tissue tumors. Cytology has long been considered inadequate as a first-line approach in this setting. However, since the implementation of new immunohistochemical and molecular tests with high diagnostic specificity, fine needle aspiration cytology (FNAC) is starting to gain acceptance for the pre-operative assessment of soft tissue tumors. FNAC represents a versatile, poorly expensive and well-tolerated diagnostic strategy with relevant advantages over histological biopsies. Moreover, evidences suggest that, in expert hands, FNAC can also aim at a definite diagnosis, especially if a cell block is prepared, allowing the application of multiple ancillary techniques.     

Malignant Smooth Muscle Tumors of the Gastrointestinal Tract: An Ultrastructural Study of 20 Cases

Twenty malignant soft tissue tumors arising from the stomach or intestine have been studied by light and electron microscopy, and the clinical records of each patient reviewed. The tumors were all considered to be of smooth muscle origin by light microscopy: Ten were spindle cell and ten were epithelioid neoplasms. By electron microscopy, only five tumors possessed smooth muscle features. A sequence of dedifferentiation could be traced among the remaining cases, indicating that the epithelioid tumors are of smooth muscle derivation. Awareness of the broad spectrum of fine structure displayed by these neoplasms will facilitate their ultrastructural identification.     

Malignant Smooth Muscle Tumors of the Gastrointestinal Tract: An Ultrastructural Study of 20 Cases

Twenty malignant soft tissue tumors arising from the stomach or intestine have been studied by light and electron microscopy, and the clinical records of each patient reviewed. The tumors were all considered to be of smooth muscle origin by light microscopy: Ten were spindle cell and ten were epithelioid neoplasms. By electron microscopy, only five tumors possessed smooth muscle features. A sequence of dedifferentiation could be traced among the remaining cases, indicating that the epithelioid tumors are of smooth muscle derivation. Awareness of the broad spectrum of fine structure displayed by these neoplasms will facilitate their ultrastructural identification.     

骨与软组织肿瘤诊断方法的研究

骨与软组织肿瘤是骨科常见疾病,对患者的生活质量、生命健康造成严重威胁。其诊断方法是临床和基础研究的重点,尤其是伴随着分子生物学技术的进步,对骨与软组织肿瘤的发生机制的认识不断深入,诊断方法也在逐步改进,但病理学检测仍是该病诊断的“金标准”。本文将对骨与软组织肿瘤的诊断方法研究进展作一综述。     

Detection of specific genetic abnormalities by fluorescence in situ hybridization in soft tissue tumors

For the detection of chromosome translocations/chimeric genes and specific genetic abnormalities in soft tissue tumors, we conducted fluorescence in situ hybridization (FISH) analysis on 280 cases of soft tissue and other tumors using formalin-fixed paraffin-embedded tissue sections. The detection rate of the FISH split-signal was 84% (129/154 cases) for the translocation-associated soft tissue tumors, such as Ewing's sarcoma/primitive neuroectodermal tumor, synovial sarcoma, alveolar rhabdomyosarcoma, myxoid liposarcoma, clear cell sarcoma and so forth. Positive split-signals from EWSR1, SS18 and FOXO1A probes were detected in 3% (2/64) of various histological types of carcinoma, lymphoma, melanoma, meningioma and soft tissue tumors. In FISH using the INI1/CEP22 probe, the INI1 deletion signal was detected in 100% (9/9) of epithelioid sarcoma. In well-differentiated and dedifferentiated liposarcomas, detection of MDM2 amplification signals in FISH using the MDM2/CEP12 probe were both as high as 85% (11/13) and 100% (13/13), respectively. In other adipocytic and non-adipocytic tumors requiring differentiation from these types, detection was only 13% (5/39), and CEP12 polysomy was frequently detected. As these results demonstrate the high sensitivity and specificity of FISH, we concluded FISH to be a useful pathological diagnostic adjunct for definite and differential diagnosis of soft tissue tumors.     

Recommendations for the reporting of soft tissue sarcoma

 The Association of Directors of Anatomic and Surgical Pathology has developed recommendations for the surgical pathology reporting of common malignant tumors. The recommendations for soft tissue sarcomas are reported herein. Received: 14 August 1998 / Accepted: 9 November 1998     

Giant adrenal myelolipoma: case report and review of the literature

Myelolipoma is a tumor-like growth composed of mature fat tissue and bone marrow elements. It occurs in the adrenal gland or as an isolated soft tissue mass. It may be associated with endocrine disorders such as hermaphroditism, Cushing's disease, Addison's disease and obesity of unknown cause. These lesions rarely measure more than 5 cm in diameter, although giant tumors have been reported in the literature. The fifth largest surgically resected adrenal myelolipoma in the literature is reported and its clinical associations and, macroscopic and microscopic features are discussed.     

软组织肿瘤细胞中的微丝结构

用透射电镜观察了一组18例肿瘤细胞胞浆中有微丝结构的软组织恶性肿瘤,电镜观察结果与光镜诊断不同,主要发生在纤维肉瘤、平滑肌肉瘤和恶性纤维组织细胞瘤中。肿瘤细胞膜下的具有密体的带状微丝可见于上述各种肿瘤中。一些肿瘤细胞也具有特征性的微丝结构。说明上述肿瘤的细胞成分有重叠。提出肿瘤的分类应主要依据大多数肿瘤细胞的分化方向来确定而不是臆测其组织发生和细胞来源。按此方法分类将会出现更多的纤维组织细胞瘤、肌纤维母细胞瘤和肌纤维组织细胞瘤的诊断。     

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.     

Recognizing hidden phenotypes in sarcomas through the electron microscope

Differentiation along a distinct cell lineage can be identified either morphologically or with the adjunct of different ancillary techniques. While immunohistochemistry has progressively supplanted electron microscopy as the method of choice to characterize the phenotype of neoplastic cells in soft tissue tumors and in solving most differential diagnoses, a number of lesions still lack reliable specific markers or show overlapping antigen expression, which can be categorized by ultrastructural analysis through the recognition of submicroscopic features indicative of a specific line of differentiation. This review discusses the role of electron microscopy in the identification of the phenotype of neoplastic cells in soft tissue sarcomas, with particular reference to the diagnostic aspects. Sarcomas in which the cellular phenotype that can be better recognized by electron microscopy include those belonging to the fibroblastic/myofibroblastic group, particularly those displaying a poorly differentiated/pleomorphic morphology. Occasionally, in tumors with smooth muscle, skeletal muscle, adipocytic, vascular endothelial, and Schwann cell differentiation electron microscopy may help in the differential diagnosis.     

Recognizing Hidden Phenotypes in Sarcomas Through the Electron Microscope

Differentiation along a distinct cell lineage can be identified either morphologically or with the adjunct of different ancillary techniques. While immunohistochemistry has progressively supplanted electron microscopy as the method of choice to characterize the phenotype of neoplastic cells in soft tissue tumors and in solving most differential diagnoses, a number of lesions still lack reliable specific markers or show overlapping antigen expression, which can be categorized by ultrastructural analysis through the recognition of submicroscopic features indicative of a specific line of differentiation. This review discusses the role of electron microscopy in the identification of the phenotype of neoplastic cells in soft tissue sarcomas, with particular reference to the diagnostic aspects. Sarcomas in which the cellular phenotype that can be better recognized by electron microscopy include those belonging to the fibroblastic/myofibroblastic group, particularly those displaying a poorly differentiated/pleomorphic morphology. Occasionally, in tumors with smooth muscle, skeletal muscle, adipocytic, vascular endothelial, and Schwann cell differentiation electron microscopy may help in the differential diagnosis.     

Ultrastructure of Abnormal Collagen in Human Tumors

Abnormal collagen fibrils were identified by transmission electron microscopy in 22 human tumors of differing histogenesis. They were found in a review of 1400 electron microscopy cases. Abnormal collagen fibrils, described by others as amianthoid fibers, composite collagen, collagen flowers and intrafibrillar collagen dysplasia, have been found only rarely in human tumors but commonly in certain connective tissue diseases such as pseudoxanthoma elasticum, Ehlers-Danlos syndromes, Marfan's syndrome, osteoarthritic cartilage, and emphysematous lung among others. Abnormalities in the cases described here included thickened fibrils, fibrillar degeneration of fibrils and irregular external contours. Proposed mechanisms for their formation have included degeneration possibly due to hypoxia or collagenase activity, abnormal collagen biosynthesis, and abnormal tissue levels of glycosaminoglycans. The finding of abnormal collagen fibrils in these 22 human tumors shows that their occurrence is more common than is indicated by previous published reports. Most of the tumors containing abnormal collagen fibrils were mesenchymal or soft tissue tumors. Four neuroendocrine neoplasms had abnormal collagen fibrils.     

Neurofibromatosis type 1 and malignancy in childhood

Neurofibromatosis type 1 (NF1) is an autosomal dominant hereditary neurocutaneous syndrome characterized by multi‐system involvement and an increased incidence of both benign and malignant tumors. In this study, we evaluated the clinical presentation and prognosis of NF1 and malignancy. Between 1975 and 2013, 26 (5%) of the 473 patients with NF1 at our center developed non‐neurofibroma neoplasms. The patient files of 26 subjects with tumors, other than optic glioma, were analyzed retrospectively to evaluate clinical features and treatment results. The age at diagnosis of NF1 ranged from 3 months to 16 years (median 5.5 years). The age range at tumor diagnosis was 1.5–33 years (median 8 years) in these 26 patients. The tumor histological subtypes included the following: 12 soft‐tissue tumors (6 malignant peripheral nerve sheath tumors (MPNST), 5 rhabdomyosarcomas (RMS) and 1 malignant fibrous histiocytoma), 11 brain tumors (6 low‐grade gliomas, 3 high‐grade gliomas, and 2 medulloblastoma), 2 neuroblastomas and 1 non‐Hodgkin's lymphoma. Twelve of 26 patients were alive at the time of the study. Although benign brain tumors with NF1 are more common, high‐grade brain tumors also occur. Thus, careful and regular follow‐up is crucial for early detection of malignancy in NF1 patients.     

A morphologic and molecular reappraisal of myoepithelial tumors of soft tissue,bone, and viscera with EWSR1 and FUS gene rearrangements

Myoepithelial tumors (MET) represent a clinicopathologically heterogeneous group of tumors, ranging from benign to highly aggressive lesions. Although MET arising in soft tissue, bone, or viscera share morphologic and immunophenotypic overlap with their salivary gland and cutaneous counterparts, there is still controversy regarding their genetic relationship. Half of MET of soft tissue and bone harbor EWSR1 or FUS related fusions, while MET arising in the salivary gland and skin often show PLAG1 and HMGA2 gene rearrangements. Regardless of the site of origin, the gold standard in diagnosing a MET relies on demonstrating its “myoepithelial immunophenotype” of positivity for EMA/CK and S100 protein or GFAP. However, the morphologic spectrum of MET in soft tissue and bone is quite broad and the above immunoprofile is nonspecific, being shared by other pathogenetically unrelated neoplasms. Moreover, rare MET lack a diagnostic immunoprofile but shows instead the characteristic gene fusions. In this study, we analyzed a large cohort of 66 MET with EWSR1 and FUS gene rearrangements spanning various clinical presentations, to better define their morphologic spectrum and establish relevant pathologic‐molecular correlations. Genetic analysis was carried out by FISH for EWSR1/FUS rearrangements and potential partners, and/or by targeted RNA sequencing. Then, 82% showed EWSR1 rearrangement, while 18% had FUS abnormalities. EWSR1‐POU5F1 occurred with predilection in malignant MET in children and young adults and these tumors had nested epithelioid morphology and clear cytoplasm. In contrast, EWSR1/FUS‐PBX1/3 fusions were associated with benign and sclerotic spindle cell morphology. Tumors with EWSR1‐KLF17 showed chordoma‐like morphology. Our results demonstrate striking morphologic‐molecular correlations in MET of bone, soft tissue and viscera, which might have implications in their clinical behavior.     

Loss of KAI1/CD82 expression in bone and soft tissue tumors is not associated with lung metastasis

The KAI1 gene has been identified as a metastasis suppressor gene in human prostate cancer. Decrease or loss of KAI1/CD82 expression has been shown to be associated with poorer prognosis and metastasis in carcinomas of various organs. The purpose of this study was to examine whether KAI1/CD82 is expressed in bone and soft tissue tumors, and whether it is associated with metastasis to the lungs. Immunohistochemically, KAI1/CD82 expression in benign and malignant soft tissue tumors was noted in 83% and 37% of cases, respectively. KAI1/CD82 was- also expressed in benign bone tumors and osteosarcomas in 67% and 36% of the cases, respectively. Four (40%) of 10 osteosarcoma cases with no lung metastasis and one (25%) of four osteosarcoma cases with lung metastasis were positive for KAI1/CD82, respectively. Metastasis of osteosarcoma cells to the lungs was not correlated with the loss of KAI1/CD82 in osteosarcoma cells.     

Doing more with less: New markers for sarcoma diagnosis and their applicability to cytology specimens

Sarcomas are a rare and extremely diverse set of neoplasms that are often a challenge to diagnose for pathologists. For a number of reasons, primary diagnosis of soft tissue neoplasms is increasingly being performed on small biopsy specimens including fine needle aspiration (FNA) and core needle biopsy (CNB). In the last several years, there has been a significant increase in our understanding of the molecular pathogenesis of this group of tumors. New insights into the genetic mechanisms of tumor formation have been exploited to create a new generation of diagnostic markers that are accessible to most laboratories. This review describes a number of new ancillary markers, and how they can facilitate accurate diagnosis of soft tissue neoplasms on FNA/CNB. Diagn. Cytopathol. 2016;44:351–360. © 2016 Wiley Periodicals, Inc.     

Stem cell transcription factor SOX2 in synovial sarcoma and other soft tissue tumors

Background

SOX2 has gained considerable interest as a pluripotency inducing gene. Co-transfection of SOX2 together with NANOG, KLF4 and c-MYC into adult fibroblasts was able to generate pluripotent stem cells. SOX2 has been reported to be expressed in synovial sarcoma, a tumor being characterized by the SS18-SSX gene fusion forming part of the SWI/SNF chromatin remodeling complex that affects histone methylation. The role of SOX2 in this tumor type as well as other soft tissue tumor entities however is still poorly characterized. We analyzed SOX2 protein expression in soft tissue tumors. Alongside we tested Histone H3 expression (H3K27me3) in SOX2 positive cases to investigate this epigenetic mark and its correlation with the SOX2 status and clinicopathological parameters.

Diagnosis of soft tissue tumors by fine-needle aspiration with combined cytopathology and ancillary techniques

The diagnosis of mesenchymal neoplasm by fine-needle aspiration biopsy (FNAB) has presented a diagnostic challenge. Most reports claim an accuracy approaching 95%, but while they distinguish benign and malignant lesions, the most problematic group, the intermediary malignant group, is omitted. The purpose of this study was to determine whether rapid cytologic diagnosis of soft-tissue tumors could guide surgeons in therapeutic decisions without the need for a tissue biopsy. Ninety-four FNA cytologic specimens were examined by the National Soft Tissue Consortium of Hungary and compared with the corresponding histology. Ordinary lipomas were excluded. Morphologic evaluation was supplemented by ancillary techniques such as fluorescence in situ hybridization (FISH), DNA cytometry, and immunocytochemistry. From a practical clinicopathological point of view, the cases were grouped in the following categories: 1) tumors with definitive diagnosis: a) high-grade malignant neoplasms (high-grade sarcomas, metastatic carcinomas, lymphoma), b) tumors with precise histogenetic origin by cytogenetics, c) benign tumors; 2) tumors of questionable nature. In the first group there were 74 tumors: 22 high-grade sarcomas, six metastatic carcinomas, one malignant lymphoma, 16 malignant tumors in which the precise histogenetic origin could be established by cytogenetic studies, and 29 benign soft-tissue tumors other than lipomas. In the second group there were 20 tumors comprising benign and malignant soft tissue tumors of low grade, wherein the precise nature of the neoplasm could not be established with confidence on cytologic study, even using ancillary techniques. FNAB of soft-tissue tumors combined with ancillary techniques should be considered a viable diagnostic technique for therapeutic protocols. Although the second group is fairly large, we have reliable, well-characterized categories which provide great freedom for preoperative and surgical treatment, thus providing the best chance for healing.     

Collagen-rich tumors of soft tissues: an overview

Although relatively common, soft tissue tumors frequently present diagnostic problems for practicing pathologists. Immunohistochemistry has facilitated the diagnosis of many mesenchymal tumors; however, there is considerable overlap in the staining profiles among cells demonstrating fibroblastic and myofibroblastic differentiation. It has been our experience that soft tissue tumors associated with abundant extracellular collagen deposition commonly cause problems in classification. One reason for this is that tumors displaying this morphology include representatives from different histogenetic families. Specifically, tumors exhibiting fibroblastic, myofibroblastic and even lipomatous differentiation may manifest as a densely collagenous mass. It is the purpose of this review to highlight these collagen-rich soft tissue tumors.