The comparative role of immunohistochemistry and electron microscopy in the identification of myogenic differentiation in soft tissue pleomorphic sarcomas

There is increasing evidence that histological classification of pleomorphic soft tissue sarcomas is prognostically useful, since a number of studies have provided evidence that myogenic differentiation is associated with a more aggressive clinical behavior. The aim of the current study was to analyze the role of electron microscopy in comparison with immunohistochemistry in the classification of soft tissue pleomorphic sarcomas. Thirty-nine pleomorphic sarcomas of the somatic soft tissues for which material for immunohistochemical and ultrastructural analysis was available were selected for this study. Cases were classified according to the criteria of the WHO classification of soft tissue tumors on the basis of the histologic appearance and of the results of immunohistochemical analysis, and then diagnoses were reconsidered at the light of the results of the ultrastructural analysis. The group of myogenic sarcomas included 13 leiomyosarcomas, 8 myofibrosarcomas, and 1 rhabdomyosarcoma, while the group of nonmyogenic sarcomas included 11 undifferentiated pleomorphic sarcomas/malignant fibrous histiocytomas (MFH), 4 myxofibrosarcomas, and 2 liposarcomas. Overall, there was a good concordance between immunohistochemistry and electron microscopy in recognizing myogenic differentiation in soft tissue pleomorphic sarcomas. Discrepancies included 1 case showing no immunoreactivity for muscle markers, which displayed ultrastructural features allowing reclassification as leiomyosarcoma, and 2 cases initially classified as undifferentiated pleomorphic sarcoma/MFH, which were reclassified as myofibrosarcomas after ultrastructural analysis. Ultrastructural analysis allowed the identification of pleomorphic sarcomas with myofibroblastic phenotype, a category that is not identifiable based on histologic and immunohistochemical profile. Notably, fibronexus junction was identified in tumor cells of 4 pleomorphic myofibrosarcomas, while 2 other lesions showed putative fibronexus junction structures, consisting of electron-dense straight fibrils adjacent to the cell surface, not clearly in continuity with cytoplasmic actin filaments. In conclusion, the results indicate that immunohistochemistry and electron microscopy can usefully complement each other in the classification of soft tissue pleomorphic sarcomas.     

Diagnostic immunohistochemistry in neuromuscular disorders

Most neuromuscular disorders display only non-specific myopathological features in routine histological preparations. However, a number of proteins, including sarcolemmal, sarcomeric, and nuclear proteins as well as enzymes with defects responsible for neuromuscular disorders, have been identified during the past two decades, allowing a more specific and firm diagnosis of muscle diseases. Identification of protein defects relies predominantly on immunohistochemical preparations and on Western blot analysis. While immunohistochemistry is very useful in identifying abnormal expression of primary protein abnormalities in recessive conditions, it is less helpful in detecting primary defects in dominantly inherited disorders. Abnormal immunohistochemical expression patterns can be confirmed by Western blot analysis which may also be informative in dominant disorders, although its role has yet to be established. Besides identification of specific protein defects, immunohistochemistry is also helpful in the differentiation of inflammatory myopathies by subtyping cellular infiltrates and demonstrating up-regulation of subtle immunological parameters such as cell adhesion molecules. The role of immunohistochemistry in denervating disorders, however, remains controversial in the absence of a reliable marker of muscle fibre denervation. Nevertheless, as well as the diagnostic value of immunocytochemical analysis it may also widen understanding of muscle fibre pathology as well as help in the development of therapeutic strategies.     

Diagnostic immunohistochemistry of breast epithelial lesions

Routine H&E sections are sufficient for diagnosis of the vast majority of breast lesions. Development of mammography mass screening and widespread use of preoperative needle biopsy diagnosis have led to diagnostic difficulties for pathologists. The samples are smaller and more and more preinvasive lesions are seen. It is mainly in those situations that immunohistochemistry (IHC) can efficiently back up histopathology. This review details the main applications of diagnostic IHC in breast pathology. The advantages of IHC in various clinical situations are discussed diagnosis of benign breast lesions mimicking malignancy, distinction between simple type ductal hyperplasia and atypical hyperplasia or ductal in situ carcinoma, confirmation of malignancy, distinction between lobular and ductal carcinoma, identification of specific histological subtypes, and, diagnosis of intra and extra mammary metastases.     

Diagnostic use of immunohistochemistry in uterine mesenchymal tumors

Immunohistochemistry may be helpful in the diagnosis of mesenchymal uterine tumors. This article reviews the immunoreactions used most frequently in the diagnosis of uterine smooth muscle tumors, endometrial stromal tumors, undifferentiated endometrial sarcomas, UTROSCTs, PEComas, adenomyomas, adenosarcomas and carcinosarcomas.     

The role of electron microscopy in the diagnosis of pleomorphic sarcomas of soft tissue

Classification of pleomorphic malignancies is frequently problematic and important with regard to treatment. Their histologic differential diagnosis is extremely wide, including sarcomatoid carcinoma, melanoma, anaplastic lymphoma, and a large number of sarcomas with overlapping light microscopic appearances. Not infrequently, immunohistochemical investigations of such tumors yield conflicting or confusing results. In such cases, electron microscopy remains an invaluable investigative and diagnostic adjunct, revealing certain subcellular features that indicate a specific line of differentiation. Combining ultrastructural and immunohistochemical studies is particularly useful in these tumors. This article focuses on the ultrastructural aspects of certain sarcomas that are predominantly pleomorphic, including high-grade fibrosarcoma, myxofibrosarcoma-malignant fibrous histiocytoma, acral myxoinflammatory fibroblastic sarcoma, pleomorphic liposarcoma, pleomorphic leiomyosarcoma, and pleomorphic rhabdomyosarcoma, as well as certain sarcomas that are occasionally quite pleomorphic, including angiosarcoma, malignant granular cell tumor, alveolar soft part sarcoma, and extraskeletal osteosarcoma. We also briefly comment on the common simulators of pleomorphic sarcomas, including melanoma, carcinoma, and lymphoma.     

34例滑膜肉瘤分子遗传学改变的诊断学意义

目的 探讨石蜡包埋滑膜肉瘤组织中t(x；18)(p11．2；q11．2)染色体易位融合基因SYT-SSX mRNA表达的诊断学意义和应用价值。方法 收集滑膜肉瘤标本34例，以14例梭形细胞肉瘤和小圆细胞肉瘤做对照(包括2例纤维肉瘤、2例平滑肌肉瘤、1例恶性神经鞘膜瘤、4例Ewing肉瘤、2例腺泡型横纹肌肉瘤、2例恶性黑色素瘤、1例血管外皮瘤)。在进行免疫组织化学指标检测的基础上，用一步法逆转录-聚合酶链反应(RT-PCR)技术检测34例石蜡包埋滑膜肉瘤组织中SYT-SSX的表达。结果 34例滑膜肉瘤中30例获得有效RNA，28例(93．3％)检出SYT-SSX融合基因表达。其中14例表达SYT-SSXl型者中10例为双相型，9例表达SYT-SSX2型者中5例为单相分化型，5例SYT-SSXl／2均未检出。对照组均未检出SYT-SSX基因的表达。结论 SYT-SSX融合基因表达可作为诊断滑膜肉瘤新的分子诊断指标。一步法RT-PCR是一种理想而可行的用于石蜡包埋滑膜肉瘤组织SYT-SSX融合基因检测的分子诊断技术。     

Diagnostic aspect of spindle-cell sarcomas by electron microscopy

Spindle-cell sarcomas in the somatic soft tissue and soft parts, including fibrosarcoma, leiomyosarcoma, malignant fibrous histiocytoma (MFH), and malignant schwannoma were examined by electron microscopy in order to delineate the most reliable cellular features for their diagnosis. Fibrosarcoma consisted largely of fibroblastic cells and leiomyosarcoma cells were packed in forming small cell groups with constant junctional complexes of nexus and zonula adherens types. MFH showed variable cellular features containing the cells with myofibroblastic and histiocytic differentiation. Malignant schwannoma was characterized by tumor cells having slender cytoplasmic processes with overlapping or interdigitation and thick basement membrane. These ultrastructural features were contributory to the differential diagnosis of the sarcomas examined.     

Diagnostic parameters of vascular neoplasms by immunohistochemistry.

Immunohistochemical identification of Factor VIII-related antigen and Ulex Europaeus A-I lectin as endothelial markers were studied in a series of 103 cases, comprising of benign and malignant vascular tumours, and few undifferentiated sarcomas. The results are correlated with that of others in this area and emphasizes the utility of these markers in surgical pathological diagnosis, especially to confirm the difficult diagnosis of angiosarcoma from other poorly differentiated sarcomas.     

Diagnostic utility of CD56 immunohistochemistry in papillary carcinoma of the thyroid

Diagnosis of papillary thyroid carcinoma (PTC), in many but not all cases, is an easily achievable diagnosis with almost minimal interobservable variability between pathologists. However, some cases of PTC, particularly the follicular variant, are quite challenging and show wide interobservable variability even among expert thyroid pathologists. Since proper diagnosis of PTC is crucial as it affects patients’ clinical management and prognosis, indications of PTC must be clearly apparent to be an objective rather than a subjective diagnosis. Unfortunately, to date, immunohistochemistry and molecular studies have failed to fully solve this problem. In this study, we assessed the protein expression and loss using antibodies against CD56 in normal follicular thyroid epithelium, follicular thyroid lesions, and follicular thyroid neoplasms in an attempt to evaluate its diagnostic value. A total of 185 cases were studied with tissues from 75 carcinomas (72 papillary, 2 follicular, 1 Hürthle cell) and 35 adenomas (32 follicular and 3 Hürthle cell) evaluated by immunohistochemistry for the expression of this marker. Non-neoplastic thyroids included 65 cases: nodular hyperplasia (n=25), thyrotoxic hyperplasia (Grave's disease) (n=5), lymphocytic thyroiditis (n=19), and Hashimoto's thyroiditis (n=6). Ten cases of normal thyroids from radical laryngectomies for laryngeal squamous cell carcinomas were also studied.     

Diagnostic role of DOG1 and p63 immunohistochemistry in salivary gland carcinomas

Background: The differential diagnosis of salivary carcinomas is always difficult and challenging. Salivary neoplasms often shows more than one growth pattern and significant morphologic variability may exist within a single tumor and between different tumors. The aim of this study was to examine the role of DOG1 (discovered on gastrointestinal tumor-1) and p63 immunohistochemistry in the diagnosis and differential diagnosis of salivary carcinomas. Methods: we examined the expression of DOG1 and p63 immunohistochemistry in 33 mucoepidermoid carcinomas (MEC), 9 acinic cell carcinomas (ACC), 10 adenoid cystic carcinomas (AdCC) and 4 myoepithelial carcinomas. Results: All ACC showed strong to moderate positivity for DOG1 (P=0.001) and all were totally negative for p63. All MEC expressed strong to moderate positivity for p63 (P=0.001) while only (9.1%) were weak to moderately positive for DOG1. (80%) AdCC were moderately positive for DOG1 in ductal and myoepithelial components and (100%) showed moderate positivity for p63 in myoepithelial cells only (P=0.001). All myoepithelial carcinomas were DOG1 negative, 2 (50%) were weakly positive for p63 while the other 2 were moderately positive (P=0.5). Conclusion: DOG1 is a sensitive marker in the diagnosis of acinic cell carcinoma, p63 is sensitive in the diagnosis of mucoepidermoid carcinoma, the combined use of both markers is helpful and statistically significant in the differential diagnosis of acinic cell carcinoma versus mucoepidermoid carcinoma, both markers can help in the diagnosis of adenoid cystic carcinoma but they have no role in the diagnosis of myoepithelial carcinoma.