Immunohistochemistry in Diagnosis of Soft Tissue Tumours
|
|
- Caren Mae Byrd
- 6 years ago
- Views:
Transcription
1 Immunohistochemistry in Diagnosis of Soft Tissue Tumours Cyril Fisher To cite this version: Cyril Fisher. Immunohistochemistry in Diagnosis of Soft Tissue Tumours. Histopathology, Wiley, 2010, 58 (7), pp < /j x>. <hal > HAL Id: hal Submitted on 6 Aug 2011 HAL is a multi-disciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.
2 Histopathology Immunohistochemistry in Diagnosis of Soft Tissue Tumours Journal: Histopathology Manuscript ID: HISTOP Wiley - Manuscript type: Review Date Submitted by the Author: 01-Aug-2010 Complete List of Authors: fisher, cyril; royal marsden hospital, histopathology Keywords: soft tissue tumours, immunohistochemistry, sarcoma, diagnosis
3 Page 1 of 39 Histopathology Immunohistochemistry in Diagnosis of Soft Tissue Tumours Cyril Fisher Royal Marsden Hospital, London UK Correspondence to: Prof Cyril Fisher MD DSc FRCPath Dept of Histopathology The Royal Marsden Hospital 203 Fulham Road London SW3 6JJ UK cyrilfisher@gmail.com Tel: Fax Running Title: Soft Tissue Tumour Immunohistochemistry Key Words Immunohistochemistry, sarcoma, diagnosis, soft tissue tumour 1
4 Histopathology Page 2 of 39 Abstract Immunohistochemistry in soft tissue tumours, and especially sarcomas, is used to identify differentiation in the neoplastic cells. In some cases, specific antigens are expressed; however, an initial panel of antibodies is often required in order to establish the broad lineage, with a subsequent, more focussed panel to allow classification. Immunohistochemical evaluation must be employed with the clinical picture, the morphology, and, when necessary, other ancillary techniques such as molecular genetics and cytogenetics. While some diagnoses are evident on morphology, many soft tissue neoplasms are seen microscopically as spindle cell, epithelioid cell, small round cell or pleomorphic tumours which need further to be characterized. This article reviews selected applications of immunohistochemistry in diagnosis of each of the principal morphological groups, concentrating on areas of most use in daily practice. 2
5 Page 3 of 39 Histopathology Introduction Soft tissue tumours comprise numerous different tumour types that are classified according to the type of mesenchymal tissue which they resemble. The main object of immunohistochemistry in soft tissue neoplasms, and especially sarcomas, is to identify differentiation in the neoplastic cells. This is straightforward for those tumours that correspond to normal tissue types, but less so for those sarcomas characterized by specific chromosomal translocations since they represent novel lineages. In some cases, specific antigens are expressed; however, an initial panel of antibodies is often required in order to establish the broad lineage, with a subsequent, more focused panel to allow precise classification. Tumours with adipocytic or osteochondroid differentiation or vascular space formation can often be recognized from the light microscopic appearances. Many soft tissue neoplasms, however, show spindle cell, epithelioid cell, small round cell or pleomorphic morphology on initial examination and require further characterisation by immunohistochemistry, electron microscopy (although this now has a limited role 1 ), and genetic analysis. This article reviews selected applications of immunohistochemistry in diagnosis in each of the principal morphological groups, concentrating on areas of most use in daily practice. It is important to remember that immunohistochemical evaluation must be employed with the clinical picture, the morphology, and, when necessary, other ancillary techniques such as molecular genetics and cytogenetics. Spindle Cell Tumours BENIGN SPINDLE CELL NEOPLASMS 3
6 Histopathology Page 4 of 39 The differential diagnosis of the principal benign soft tissue tumours is straightforward when the lineage is obvious. Difficulty is sometimes encountered, especially in core biopsies, in assessing malignancy, the morphological criteria for which vary according to the tumour type. In specific situations, immunohistochemistry is occasionally of assistance in distinguishing benign from malignant lesions. For example, diffuse S100 protein positivity in a spindled nerve sheath tumour is more suggestive of schwannoma than malignant peripheral nerve sheath tumour (MPNST), especially if there are portions of capsule in the biopsy. Recently, it has been suggested that a rare CD34-positive cellular fibrous histiocytoma can be distinguished from the commonly CD34-positive dermatofibrosarcoma by the expression of podoplanin (D2-40) in the former but not the latter. 2 Combinations of CD34 with other antibodies can be useful in selected circumstances (Table 1). Cell cycle-related and proliferation markers are of little use in individual cases. The proliferation index with Ki67 can be indicative of malignancy when high, but it can also be high in reactive lesions such as nodular fasciitis. INTERMEDIATE SPINDLE CELL NEOPLASMS Fibromatosis is a non-metastasizing lesion which is a consideration in the differential diagnostic of many types of spindle cell sarcoma. The lesional cells are myofibroblasts which are focally positive for smooth muscle actin (SMA) and occasionally for desmin in scattered cells. S100 protein can be focally positive but CD34 is negative. Nuclear immunoreactivity for beta-catenin is found in variable numbers of nuclei in about 80% of deep fibromatoses, but only 5% of superficial ones. 3, 4 Non-specific paranuclear staining is common in other myofibroblastic lesions and must not be misinterpreted. Nuclear 4
7 Page 5 of 39 Histopathology beta-catenin positivity can also be found in about 40% of solitary fibrous tumours, synovial sarcomas and endometrial stromal sarcomas, as well as in hypertrophic scars. It is absent from gastrointestinal stromal tumour, leiomyosarcoma, inflammatory myofibroblastic tumour and MPNST, which is of use in the differential diagnosis of intraabdominal spindle cell neoplasms. 5 Conversely, fibromatosis is negative for h- caldesmon, ALK, CD34, CD117 and DOG1. Solitary fibrous tumour is diffusely positive for CD34 in 95% of cases, as well as for bcl-2, CD99 and beta-catenin. 3, 6-8 Occasional cells expressing cytokeratin (CK), 9 epithelial membrane antigen (EMA), or S100 protein can be seen, which does not alter the diagnosis. Malignant solitary fibrous tumour, manifesting as spindle or polygonal cell sarcoma contiguous with (or recurrent at the site of a previous) typical solitary 10, 11,12 fibrous tumour, usually retains CD34 expression diffusely or focally. Angiomatoid fibrous histiocytoma expresses desmin in about 50% of cases, but myogenin is negative. Other antigens that are sometimes positive are h-caldesmon, SMA (but the morphology is unlike that of smooth muscle tumours), CD99 and EMA. 13 This tumour has three translocations resulting in the fusion genes EWSR1-CREB1 (the commonest), EWSR1-ATF1, or FUS-ATF1. 14 The first two are shared with clear cell sarcoma (see below). MALIGNANT SPINDLE CELL NEOPLASMS These include synovial sarcoma, malignant peripheral nerve sheath tumour, leiomyosarcoma, myofibrosarcoma and fibrosarcoma, and spindle cell variants of rhabdomyosarcoma and angiosarcoma. Non-mesenchymal tumours such as sarcomatoid 5
8 Histopathology Page 6 of 39 carcinoma, melanoma and follicular dendritic cell sarcoma can present in soft tissue locations and thereby enter the differential diagnosis. Synovial sarcoma is diagnostically obvious when biphasic. The monophasic form is a spindle cell sarcoma composed of closely packed uniform cells with overlapping nuclei and scanty cytoplasm, while poorly differentiated synovial sarcoma has polygonal or small round cells with high proliferation index. 15 All types of synovial sarcoma exhibit epithelial differentiation with focal positivity for cytokeratins (including CK7 and CK19) and for EMA in most cases. Diffuse expression of bcl-2 and focal positivity for CD99, S100 protein, CD56 and calponin are also found in some, and other non-specific markers of occasional diagnostic value include beta-catenin (nuclear) 3 and calretinin (nuclear). 16 CD34 is almost always negative in synovial sarcoma 17 which is useful in excluding solitary fibrous tumour, since the immunophenotype of these two tumours can otherwise overlap. TLE1, an antibody derived from gene expression profiling studies, is emerging as a highly sensitive (nuclear) marker for synovial sarcoma of all morphologic 18, 19 types. It is also not wholly specific, since occasional examples of nerve sheath tumours can display positivity. However, its sensitivity means that it is useful in excluding the diagnosis of synovial sarcoma when the result is negative. Reduced expression of INI1 (see below) has been described in some synovial sarcomas. 20 Synovial sarcoma is characterized by a specific chromosomal translocation t(x;18)(p11.2;q11.2), which results in fusion of the SS18 (SYT) gene from chromosome 18 with one of several variants of the SSX gene on the X chromosome. 21 Recently, an antibody to the SS18 gene product has been shown to be sensitive for identification of synovial sarcoma but it is not specific and has not found general application. 22 6
9 Page 7 of 39 Histopathology Malignant peripheral nerve sheath tumours (MPNST) have focal nuclear positivity for S100 protein in up to 67% of cases, which correlates with ultrastructural evidence of Schwann cell differentiation. 23 There are no other specific indicators of nerve sheath lineage (although electron microscopy can be contributory in S100 proteinnegative examples 23 ) but many MPNST are focally positive for CD34, and a variable proportion of cases express GFAP, myelin basic protein, CD57 and nestin. Cytokeratins are occasionally positive but the presence of CK7 or CK19 is more indicative of synovial sarcoma than of MPNST. 24 Immunoreactivity for NSE or PGP9.5 is sometimes found in MPNST but these markers are non-specific and of no value in diagnosis. 25 EMA positivity is occasionally seen in MPNST with Schwannian differentiation, but is most useful in diagnosis of benign perineurioma 26 and its rare malignant counterpart, 27 which usually lack S100 protein. Another useful marker of perineurial cell differentiation is claudin-1 which, as a tight junction-associated protein, 28 has a granular distribution in normal perineurial cells and in perineurioma. 29 positive in low-grade fibromyxoid sarcoma 30 Claudin-1 has also been reported as which can resemble perineurioma, especially in cutaneous lesions, so that genetic analysis (see below) can be required for diagnosis. Leiomyosarcoma is most often morphologically distinctive, with its non-tapered cells with eosinophilic cytoplasm and squared-off nuclei, arranged in cellular fascicles in a distinctive rectilinear pattern. Immunohistochemically, desmin, SMA, muscle specific actin (MSA), h-caldesmon, calponin and smooth muscle myosin (SMM) are expressed in the majority of leiomyosarcomas. Some examples co-express cytokeratins (frequently with dot pattern), EMA and S100 protein but usually only when the muscle-specific 7
10 Histopathology Page 8 of 39 antigens are present. CD99 can also be seen in a paranuclear dot pattern. CD34 expression is variable but generally negative in leiomyosarcoma, and CD117 is absent from smooth muscle tumours. A spindle cell neoplasm expressing SMA but not desmin or h-caldesmon is unlikely to be a smooth muscle tumour and is more likely to be myofibroblastic. 31 Myofibrosarcomas are spindle cell or pleomorphic sarcomas which display myofibroblastic differentiation. 32 Low grade myofibrosarcomas are composed of tapered cells containing ovoid nuclei and punctate nucleoli, arranged in sheets and fascicles. 33 They are positive for SMA (with a tram-track subplasmalemmal accentuation), and usually express calponin and less commonly desmin. H-caldesmon and SMM are negative, distinguishing myofibrosarcoma from leiomyosarcoma. 34 CD34 and S100 protein are also negative; the combination of CD34 and desmin immunoreactivity is found in mammary-type myofibroblastomas, 35 but their ultrastructure is more like that of smooth muscle cells than of true myofibroblasts. 36 Inflammatory myofibroblastic tumour (IMT) is a low-grade myofibroblastic malignancy with fasciitis-like, fascicular and sclerosing histological patterns. 37 In addition to the usual myofibroblastic markers, about half of IMT, especially those in viscera and in children, express ALK, and recent evidence suggests that lack of ALK is prognostically adverse. 38 In IMT, the ALK gene is rearranged with one of six partner genes, most of which result in cytoplasmic staining on immunohistochemistry, except for ALK-RANBP2. The latter gives a distinctive nuclear membranous distribution as RANBP2 binding proteins are localised at the nuclear pore complex. 39 8
11 Page 9 of 39 Histopathology Adult fibrosarcoma is now a rare tumour which is by definition negative for all lineage markers (fibrosarcomas express vimentin but this is a wholly non-specific marker which need not usually be included in diagnostic panels). However, specific subtypes of fibrosarcoma are positive for CD34, including those arising in dermatofibrosarcoma, about half of myxofibrosarcomas, and a smaller proportion of myxoinflammatory fibroblastic sarcomas. 40 Some superficial fibrosarcomas that are strongly CD34 positive but lack an apparent dermatofibrosarcomatous component have been shown to have the same COL1A1-PDGFRB fusion gene transcripts as dermatofibrosarcoma. 41 In a CD34- negative fibrosarcoma, an occasional SMA-positive cell can sometimes be seen which is attributable to focal myofibroblastic differentiation, but diffuse or multifocal SMA staining indicates categorization as myofibrosarcoma. 32 Low grade fibromyxoid sarcoma occasionally has SMA or CD34 positivity (and, as previously noted, can express EMA and claudin-1 30 ), but the diagnosis is best confirmed by genetic demonstration of the t(7;16)(q33;p11) or FUS-CREB3L2 (or rarely FUS-CREB3L1) fusion gene, which has also been reported in some examples of sclerosing epithelioid fibrosarcoma. 45 Spindle cell rhabdomyosarcoma of juvenile (adolescent) 46, 47 or adult type is diffusely positive for desmin, and at least focally so in nuclei for myogenin and MyoD1. The latter is less sensitive, but in the rare sclerosing pseudovascular rhabdomyosarcoma, MyoD1 is more widely expressed than myogenin. 51 It should be noted that these are nuclear antigens and that cytoplasmic staining for either is non-specific and does not denote rhabdomyoblastic differentiation. Myoglobin, a previously widely used 9
12 Histopathology Page 10 of 39 cytoplasmic marker for skeletal muscle differentiation, is of low sensitivity and specificity and is no longer recommended for routine use. Spindle cell angiosarcoma is an uncommon soft tissue sarcoma of skin or soft tissue in which diagnostic vasoformative areas can be present only focally and therefore absent from a core biopsy. The tumour can be identified by its expression of CD31, and less commonly of CD34 and other endothelial markers (see discussion of epithelioid endothelial neoplasms below). CD117 positivity has also been reported in angiosarcoma 52 and in Kaposi sarcoma (KS). The latter, however, demonstrates highly specific immunoreactivity for HHV8 (KSHV) in the nuclei of its spindled and endothelial cells, which is not found in other endothelial neoplasms. 53 Podoplanin (D2-40) is a lymphatic endothelial marker that has a membranous staining pattern in Kaposi sarcoma, but also in some angiosarcomas and gastrointestinal stromal tumours (which also display CD34 and CD117, as in angiosarcoma). 54 Antibodies to vascular endothelial growth factor and its receptor (such as VEGF-C and VEGFR-3) are also immunoreactive in 55, 56 KS. Follicular dendritic cell sarcoma (FDCS), which sometimes arises in soft tissue sites, is characterised by fascicles and whorls of cells in which the nuclei typically display prominent membranes and a speckled chromatin pattern. Immunoreactivity for CD21, CD35 (the two are more sensitive when used together as a cocktail 60 ) and CD23 is diagnostic, and other markers reportedly helpful in identifying FDCS include fascin, clusterin 61 and D Many examples are also positive for S100 protein and EMA. 63 Sarcomatoid carcinoma can express cytokeratins focally, especially those of high molecular weight, but can also be negative. 64 The diagnosis can be facilitated by finding 10
13 Page 11 of 39 Histopathology areas of epithelial differentiation or surface dysplasia, or a nested reticulin pattern. Spindle cell carcinoma can also express SMA, but desmin, h-caldesmon, CD34 and S100 protein are absent. SMA-positive/CK-negative sarcomatoid carcinoma, which is usually a pleomorphic neoplasm, can be difficult to distinguish from pleomorphic myofibrosarcoma without knowledge of the history and the location of the tumour. Gastrointestinal stromal tumours (GIST) can arise not only in the gastrointestinal tract but also in extra-gastrointestinal locations, especially omentum, mesentery and retroperitoneum. The two predominant patterns are spindled or epithelioid, which have a similar immunophenotype. GIST typically express CD117, the product of the KIT gene, which encodes a receptor tyrosine kinase, and which in GIST shows a variety of prognosis-related mutations A small number of GIST are CD117-negative, and some of these have mutations in the gene which encodes platelet-derived growth factor receptor A (PDGFRA). 67 These are often epithelioid gastric GIST. The antibody DOG1, identified by gene expression profiling, has high sensitivity and specificity for GIST and can identify most KIT-negative tumours. 68, 69 Other antigens found in GIST include CD34 in % of tumours (varying with site 70 ), SMA (varying inversely with CD34 expression), h-caldesmon, bcl-2 and, less commonly, desmin or S100 protein. Betacatenin is negative in nuclei, in contrast to fibromatosis. 5 Epithelioid and clear cell tumours Epithelioid soft tissue neoplasms include epithelioid sarcoma, and epithelioid variants of MPNST, leiomyosarcoma, and fibrosarcoma, as well as clear sarcoma, alveolar soft part sarcoma, PEComa (Table 2), and melanoma and carcinoma when presenting in soft tissue locations. 11
14 Histopathology Page 12 of 39 Epithelioid sarcoma (EpS), of both classical and proximal types, is positive for the epithelial markers cytokeratins and EMA and, in about 50% of cases for CD This is particularly useful in making the distinction from primary or metastatic carcinomas, which are CD34 negative. In addition, CK5/6, a useful marker for carcinomas especially those with squamous differentiation, is detectable in only a small proportion of epithelioid sarcomas. 72 EpS generally lacks desmin, S100 protein and FLI- 1, 73 which help in diagnosis from rhabdomyosarcoma, melanoma, and epithelioid angiosarcoma respectively. Antibodies to INI1 are negative in about 90% of EpS, in malignant rhabdoid tumours (MRT), in about half the cases of epithelioid MPNST, and in some extraskeletal myxoid chondrosarcomas with rhabdoid cytomorphology This relates to the location of the SMARC/INI gene on chromosome 22q, which is mutated or deleted in MRT and EpS. 74 Absence of INI1 is extremely useful for diagnosis of these tumours since all other epithelioid or polygonal cell tumours in the differential diagnosis display nuclear positivity for this marker. MRT can be distinguished from EpS by absence of CD34, although clinical data are required to distinguish MRT from CD34- negative EpS. Epithelioid MPNST differs from its spindle cell counterpart in displaying diffuse S100 protein expression in most cases. 77 It differs from melanoma in having more uniform cytological features, frequent association with a typical spindle cell nerve sheath component, and absence of melanoma-specific antigens. INI-negative cases should not be misdiagnosed as epithelioid sarcoma, or INI-positive cases as epithelioid angiosarcoma, since both of these tumour types are S100 protein negative. 12
15 Page 13 of 39 Histopathology Epithelioid endothelial neoplasms manifest varying combinations of vascular endothelial cell markers. These include CD34, CD31, FLI-1 (in nuclei), FVIIIRAg, thrombomodulin and CD117. In epithelioid angiosarcoma and malignant variants of epithelioid haemangioendothelioma these antigens are selectively expressed so that not all are detectable by immunohistochemistry. CD31 and FVIIIRAg are the most specific, although the latter is not very sensitive. These tumours show diffuse nuclear immunoreactivity for INI1, 76 and D2-40 is positive in some cases. 54 In addition, epithelioid angiosarcoma is frequently cytokeratin-positive, while usually lacking 78, 79 EMA. Epithelioid sarcoma, especially the proximal variant, can be morphologically similar to epithelioid angiosarcoma and can also co-express CD34 and cytokeratins, but lacks CD31, FVIIIRAg, FLI-1, and INI1. Epithelioid sarcoma-like haemangioendothelioma is a very rare low-grade spindle cell neoplasm that displays 80, 81 positivity for cytokeratins, CD31, and FL1-1, but lacks CD34 (Table 1). PEComa is the term used for a group of clinically disparate tumours composed of supposed perivascular epithelioid cells spindle or polygonal cells with clear or granular 82, 83 cytoplasm and uniform nuclei, which are arranged in nests around sinusoidal vessels. Members of the PEComa family include angiomyolipoma, lymphangioleiomyomatosis, clear cell sugar tumour of lung and other sites, and clear cell myomelanocytic tumour. PEComas co-express SMA and the melanocytic antigens HMB-45, melan-a, and microophthalmia transcription factor (MITF). It has become recognized that PEComas can also focally express S100 protein, desmin and h-caldesmon as well as TFE3 in some cases , 85 Most PEComas are benign but malignant examples are increasingly reported. The principal differential diagnosis (Table 2) is with clear sarcoma of tendons and 13
16 Histopathology Page 14 of 39 aponeuroses which also expresses melanoma-specific antigens, but which has diffuse S100 protein positivity, lacks SMA and h-caldesmon, and is characterized by a specific translocation t(12;22)(q13;q12) with fusion of EWS and ATF-1 genes. 86 The morphologically similar clear cell sarcoma of the gastrointestinal tract with osteoclastlike giant cells is also S100 protein positive but lacks melan-a and HMB45 expression, and usually has t(2;22)(q33;q12) with EWS-CREB1 fusion. 87 However, examples of both fusions have been described at both sites. 88 The same fusions are also found in angiomatoid fibrous histiocytoma, 89 representing one of several examples of promiscuity among gene fusions. 90 Alveolar soft part sarcoma has long been an enigmatic tumour in which the occasional report of immunoreactivity for desmin and, for a time, MyoD1, led to the assumption that the tumour showed skeletal muscle differentiation. This tumour, however, is now known to be a translocation-associated sarcoma characterized by t(x;17)(p11;q25) with fusion of TFE3 and ASPL genes. 91 Antibodies to TFE3 are available which demonstrate nuclear positivity in alveolar soft part sarcoma; similar staining is also found in some translocation-associated carcinomas of kidney, in some PEComas and in examples of granular cell tumour. 92 Pleomorphic tumours Pleomorphic sarcomas include liposarcoma (pleomorphic and dedifferentiated), rhabdomyosarcoma, MPNST, leiomyosarcoma, myofibrosarcoma, and undifferentiated pleomorphic sarcoma (also known as pleomorphic malignant fibrous histiocytoma or 14
17 Page 15 of 39 Histopathology MFH). Undifferentiated or sarcomatoid carcinoma, melanoma and rarely lymphoma can also have similar microscopic appearances. Pleomorphic neoplasms are composed predominantly of pleomorphic spindle, polygonal and giant cells with mitoses, necrosis and inflammation. In addition the specific subtypes have foci of differentiation perceived either morphologically (lipoblasts) or immunohistochemically (skeletal, smooth muscle, melanocytic or epithelial antigens). In many cases without apparent lineage, the pleomorphic cells have ultrastructural features of fibroblasts with a variable proportion of cells showing myofibroblastic differentiation. 93 Thus, MFH and undifferentiated areas of other pleomorphic sarcomas can display focal SMA positivity, with a characteristic subplasmalemmal linear distribution imparting a tram-track appearance. 94 Desmin positivity is occasionally seen but h-caldesmon is absent. It is important to identify pleomorphic sarcomas with any type of myogenic differentiation at immunohistochemical level since, counter-intuitively, they have a worse prognosis than 95, 96 undifferentiated pleomorphic sarcomas. Pleomorphic rhabdomyosarcoma usually has diffuse desmin positivity and focal nuclear staining for myogenin. MyoD1 is a less 51, 97 sensitive marker except in sclerosing pseudovascular rhabdomyosarcoma. In pleomorphic leiomyosarcoma, typical fascicular areas occupying <25% of the pleomorphic tumour are usually required for the diagnosis. 98 However, immunohistochemical evidence of smooth muscle differentiation (desmin, SMA and h- caldesmon) without corresponding morphological features is associated with a worse 95, 96 prognosis. MFH-like undifferentiated sarcomas with widespread SMA positivity can be termed pleomorphic myofibrosarcomas; the distinction is important since 15
18 Histopathology Page 16 of 39 myofibroblastic differentiation, although less well-studied than myoid differentiation, also appears prognostically unfavorable. 94 Dedifferentiated liposarcoma, like well differentiated liposarcoma, has MDM2 and CDK4 amplification, detectable by fluorescence in situ hybridization (FISH) and also by immunohistochemistry. 99 Most retroperitoneal (and some extremity 100 ) undifferentiated pleomorphic sarcomas (MFH) and myxofibrosarcomas express these markers (in nuclei) and are now considered to represent dedifferentiated liposarcomas even when no well-differentiated component remains In addition, dedifferentiated liposarcoma can express actin, desmin and CD34 focally in the pleomorphic areas, 101 which should not be misinterpreted as leiomyosarcoma. Sarcomatoid carcinoma can appear as a pleomorphic neoplasm. This usually expresses cytokeratins in a multifocal or diffuse distribution that is best demonstrated with a broad spectrum antibody or cytokeratin cocktail. Even very focal cytokeratin expression should prompt consideration of a primary carcinoma, and it can be accepted as evidence of epithelial differentiation in an organ-based (visceral) pleomorphic neoplasm. It should be remembered, however, that some undifferentiated pleomorphic sarcomas in soft tissue have (aberrant) expression of cytokeratin, usually in a few scattered cells. 104, 105 Also, as previously noted, spindled carcinomas can acquire myofibroblastic differentiation and thereby be focally positive for SMA (but not desmin or h-caldesmon). As always, the final diagnosis must summate all data including clinical and radiological findings. Small round cell tumours 16
19 Page 17 of 39 Histopathology This group of soft tissue neoplasms includes Ewing sarcoma/primitive neuroectodermal tumour (ES), desmoplastic small round cell tumour (DSRCT), alveolar rhabdomyosarcoma (ARMS), neuroblastoma (NB), and poorly differentiated synovial sarcoma (PDSS). Most of these occur predominantly in childhood and adolescence, but are also seen sporadically in adults. 106 Several of these sarcoma subtypes have specific, translocations and consequent fusion genes that allow precise diagnosis, and in some 90, 107 instances provide prognostic information, using FISH or PCR-based methods. A molecular pathology service is not always readily available, but the immunophenotypes of these small round cell sarcomas differ sufficiently to enable diagnosis in many cases. Lymphomas, especially of lymphoblastic type, must also be considered in the differential diagnosis, and TdT should be part of the diagnostic panel in the appropriate clinical setting. Similarly leukaemic deposits, and small cell carcinomas might need exclusion by immunostaining for myeloid markers or cytokeratins, neuroendocrine antigens and TTF1 respectively. Ewing sarcoma is a translocation-associated tumour, which can arise in bone or extraskeletal sites; examples with evidence of neural differentiation are termed PNET. 90 The large majority of ES display diffuse membranous staining for CD99, and some express neurofilament proteins and NSE. About 70% show nuclear immunoreactivity for FLI A small number are also positive for S100 protein or display dot positivity with broad spectrum anticytokeratin antibodies and membranous staining for EMA. CD56 is usually negative, unlike in small cell neuroendocrine carcinoma and PDSS. 109 The latter also expresses TLE1, but some cases have a similar immunophenotype to ES and although there are subtle morphological differences (ES tends to be more uniform and 17
20 Histopathology Page 18 of 39 lacks intercellular reticulin), genetic analysis may be required to make the diagnosis. The morphologic spectrum of ES is expanding due to increased recognition of atypical 110, 111 variants aided, in part, by molecular studies. Although there is a wide range of available antibodies at least three of a panel composed of CD99, FLI-1, HNK1, and caveolin-1 reportedly show immunoreactivity in all cases with caveolin-1 being positive in CD99-negative cases. 111 Desmoplastic small round cell tumour was originally described in the abdomen and pelvis in adolescent males, and is now recognized in other locations. It shows presumed primitive mesothelial differentiation, and has a characteristic t(11;22)(p13;q12) rearrangement with formation of an EWS-WT1 fusion gene. Immunohistochemically, DSRCT shows nuclear staining with antibodies to the C-terminal end of WT1 as well as multilineage differentiation with dot positivity for desmin, cytokeratins (CK20 and CK5/6 are negative), and neural markers including chromogranin A, synaptophysin, 112, 113 neurofilaments, and CD56. However, not all lineage markers are expressed in every case. 114 DSRCT is usually negative for CD99 but 10-20% (and especially those with variant translocations) can be positive which does not therefore exclude the 115, 116 diagnosis. Alveolar rhabdomyosarcoma, as with other rhabdomyosarcoma subtypes, has diffuse cytoplasmic staining for desmin. Myogenin is expressed in a majority of tumour cell nuclei and is more sensitive than MyoD CD56 is also positive as in other types of rhabdomyosarcoma % of ARMS have either t(2;13)(q35;q14) creating a PAX3- FOXO1 fusion gene or t(1;13)(p36;q14) with resulting PAX7-FOXO1 fusion
21 Page 19 of 39 Histopathology Immunohistochemistry with an antibody to PAX5 can detect all translocation-positive cases of either type. 119 Neuroblastoma can be recognized not only by its clinical context (the vast majority are in patients <4 years old and arise in adrenal or other sympathetic nervous system locations), but also by its expression of NB84, NSE, CD56 and neurofilament proteins. 120 Antibodies to these markers, which can be used as a panel, are particularly useful in detection of residual disease in bone marrow specimens taken after chemotherapy. Neuroblastoma is negative for cytokeratins, desmin and CD99, which can be particularly helpful in diagnosis of rare examples in adults. 121 Adipose tumours The distinction between lipoma and atypical lipomatous tumour (ALT)/well differentiated liposarcoma can be difficult since it depends on focal morphologic subtleties which are not always represented in the samples taken. The diagnosis is facilitated by the demonstration of immunohistochemical positivity for products of the murine double minute type 2 (MDM2) and cyclin-dependent kinase 4 (CDK4) genes which are overexpressed in ALT as a result of amplification in the 12q14-15 chromosomal region. All ALT are immunoreactive in nuclei for MDM2 (often focally) and 91% for CDK4 (more diffusely). 99 These have application not only in the differential diagnosis of lipoma and ALT, but also in determining whether the fatty tissue at the margin of excision of ALT is neoplastic or not. As mentioned above, in dedifferentiated liposarcoma (DDL), which is genetically related to ALT, CDK4 and MDM2 are similarly 102, 122 overexpressed. Their specificity in DDL is reduced since a small proportion of 19
22 Histopathology Page 20 of 39 MPNST, myxofibrosarcomas and embryonal rhabdomyosarcomas are immunoreactive with both 99 but, apart from morphological considerations, the diagnosis of DDL is supported by positivity for these two markers in the differentiated adipose tissue adjacent to the pleomorphic neoplasm. Conclusion Existing antibody panels, when correctly selected, have a major role in diagnosis of soft tissue sarcomas. Diagnostically useful new antibodies, such as DOG1 and TLE1, are emerging from gene profiling studies, and in addition to the usual reagents, antibodies to fusion gene products might theoretically be of value in detecting translocation sarcomas. For example, antibodies raised against TLS/EWS-CHOP chimeric oncoproteins have shown high specificity and sensitivity for myxoid and round cell liposarcoma. 123 These approaches can be expected to lead to improved diagnosis of soft tissue tumours and perhaps to more efficient use of immunohistochemistry with limited and therefore less expensive panels. Acknowledgment I acknowledge NHS funding to the NIHR Biomedical Research Centre. 20
23 Page 21 of 39 Histopathology References 1. Fisher C. The comparative roles of electron microscopy and immunohistochemistry in the diagnosis of soft tissue tumours. Histopathology 2006;48; Bandarchi B, Ma L, Marginean C, Hafezi S, Zubovits J, Rasty G. D2-40, a novel immunohistochemical marker in differentiating dermatofibroma from dermatofibrosarcoma protuberans. Mod Pathol 2010;23; Ng TL, Gown AM, Barry TS et al. Nuclear beta-catenin in mesenchymal tumors. Mod Pathol 2005;18; Bhattacharya B, Dilworth HP, Iacobuzio-Donahue C et al. Nuclear beta-catenin expression distinguishes deep fibromatosis from other benign and malignant fibroblastic and myofibroblastic lesions. Am J Surg Pathol 2005;29; Montgomery E, Torbenson MS, Kaushal M, Fisher C, Abraham SC. Beta-catenin immunohistochemistry separates mesenteric fibromatosis from gastrointestinal stromal tumor and sclerosing mesenteritis. Am J Surg Pathol 2002;26; Renshaw AA PG, Corson JM. CD34 and AE1/AE3. Diagnostic discriminants in the distinction of solitary fibrous tumor of the pleura from sarcomatoid mesothelioma. Appl Immunohistochem 1994;2; Chan JK. Solitary fibrous tumour--everywhere, and a diagnosis in vogue. Histopathology 1997;31; Chilosi M, Facchetti F, Tos APD et al. bcl-2 expression in pleural and extrapleural solitary fibrous tumours. J Pathol 1997;181;
24 Histopathology Page 22 of McGuire LJ, Chan HS, Pang J. Solitary fibrous tumor of pleura: expression of cytokeratins. Pathology 1990;22; Nielsen GP, O'Connell JX, Dickersin GR, Rosenberg AE. Solitary fibrous tumor of soft tissue: a report of 15 cases, including 5 malignant examples with light microscopic, immunohistochemical, and ultrastructural data. Mod Pathol 1997;10; Vallat-Decouvelaere AV, Dry SM, Fletcher CD. Atypical and malignant solitary fibrous tumors in extrathoracic locations: evidence of their comparability to intra-thoracic tumors. Am J Surg Pathol 1998;22; Fisher C. Low-grade sarcomas with CD34-positive fibroblasts and low-grade myofibroblastic sarcomas. Ultrastruct Pathol 2004;28; Thway K. Angiomatoid fibrous histiocytoma: a review with recent genetic findings. Arch Pathol Lab Med 2008;132; Antonescu CR, Dal Cin P, Nafa K et al. EWSR1-CREB1 is the predominant gene fusion in angiomatoid fibrous histiocytoma. Genes Chromosomes Cancer 2007;46; Fisher C. Synovial sarcoma. Ann Diagn Pathol 1998;2; Miettinen M, Limon J, Niezabitowski A, Lasota J. Calretinin and other mesothelioma markers in synovial sarcoma: analysis of antigenic similarities and differences with malignant mesothelioma. Am J Surg Pathol 2001;25; Pelmus M, Guillou L, Hostein I, Sierankowski G, Lussan C, Coindre JM. Monophasic fibrous and poorly differentiated synovial sarcoma: immunohistochemical 22
25 Page 23 of 39 Histopathology reassessment of 60 t(x;18)(syt-ssx)-positive cases. Am J Surg Pathol 2002;26; Kosemehmetoglu K, Vrana JA, Folpe AL. TLE1 expression is not specific for synovial sarcoma: a whole section study of 163 soft tissue and bone neoplasms. Mod Pathol 2009;22; Jagdis A, Rubin BP, Tubbs RR, Pacheco M, Nielsen TO. Prospective evaluation of TLE1 as a diagnostic immunohistochemical marker in synovial sarcoma. Am J Surg Pathol 2009;33; Kohashi K, Oda Y, Yamamoto H et al. Reduced expression of SMARCB1/INI1 protein in synovial sarcoma. Mod Pathol 2010;23; Ladanyi M, Antonescu CR, Leung DH et al. Impact of SYT-SSX fusion type on the clinical behavior of synovial sarcoma: a multi-institutional retrospective study of 243 patients. Cancer Res 2002;62; He R, Patel RM, Alkan S et al. Immunostaining for SYT protein discriminates synovial sarcoma from other soft tissue tumors: analysis of 146 cases. Mod Pathol 2007;20; Fisher C, Carter RL, Ramachandra S, Thomas DM. Peripheral nerve sheath differentiation in malignant soft tissue tumours: an ultrastructural and immunohistochemical study. Histopathology 1992;20; Smith TA, Machen SK, Fisher C, Goldblum JR. Usefulness of cytokeratin subsets for distinguishing monophasic synovial sarcoma from malignant peripheral nerve sheath tumor. Am J Clin Pathol 1999;112;
26 Histopathology Page 24 of Campbell LK, Thomas JR, Lamps LW, Smoller BR, Folpe AL. Protein gene product 9.5 (PGP 9.5) is not a specific marker of neural and nerve sheath tumors: an immunohistochemical study of 95 mesenchymal neoplasms. Mod Pathol 2003;16; Hornick JL, Fletcher CD. Soft tissue perineurioma: clinicopathologic analysis of 81 cases including those with atypical histologic features. Am J Surg Pathol 2005;29; Hirose T, Scheithauer BW, Sano T. Perineurial malignant peripheral nerve sheath tumor (MPNST). A clinicopathologic, immunohistochemical, and ultrastructural study of seven cases. Am J Surg Pathol 1998;22; Billings SD, Walsh SV, Fisher C, Nusrat A, Weiss SW, Folpe AL. Aberrant expression of tight junction-related proteins ZO-1, claudin-1 and occludin in synovial sarcoma: an immunohistochemical study with ultrastructural correlation. Mod Pathol 2004;17; Folpe AL, Billings SD, McKenney JK, Walsh SV, Nusrat A, Weiss SW. Expression of claudin-1, a recently described tight junction-associated protein, distinguishes soft tissue perineurioma from potential mimics. Am J Surg Pathol 2002;26; Thway K, Fisher C, Debiec-Rychter M, Calonje E. Claudin-1 is expressed in perineurioma-like low-grade fibromyxoid sarcoma. Hum Pathol 2009;40; Ceballos KM, Nielsen GP, Selig MK, O'Connell JX. Is anti-h-caldesmon useful for distinguishing smooth muscle and myofibroblastic tumors? An immunohistochemical study. Am J Clin Pathol 2000;114;
27 Page 25 of 39 Histopathology 32. Fisher C. Myofibrosarcoma. Virchows Arch 2004;445; Eyden B, Banerjee SS, Shenjere P, Fisher C. The myofibroblast and its tumours. J Clin Pathol 2009;62; Fisher C. Myofibroblastic malignancies. Adv Anat Pathol 2004;11; McMenamin ME, Fletcher CD. Mammary-type myofibroblastoma of soft tissue: a tumor closely related to spindle cell lipoma. Am J Surg Pathol 2001;25; Eyden BP, Shanks JH, Ioachim E, Ali HH, Christensen L, Howat AJ. Myofibroblastoma of breast: evidence favoring smooth-muscle rather than myofibroblastic differentiation. Ultrastruct Pathol 1999;23; Gleason BC, Hornick JL. Inflammatory myofibroblastic tumours: where are we now? J Clin Pathol 2008;61; Coffin CM, Hornick JL, Fletcher CD. Inflammatory myofibroblastic tumor: comparison of clinicopathologic, histologic, and immunohistochemical features including ALK expression in atypical and aggressive cases. Am J Surg Pathol 2007;31; Wilken N, Senecal JL, Scheer U, Dabauvalle MC. Localization of the Ran-GTP binding protein RanBP2 at the cytoplasmic side of the nuclear pore complex. Eur J Cell Biol 1995;68; Meis-Kindblom JM, Kindblom LG. Acral myxoinflammatory fibroblastic sarcoma: a low-grade tumor of the hands and feet. Am J Surg Pathol 1998;22; Sheng WQ, Hashimoto H, Okamoto S et al. Expression of COL1A1-PDGFB fusion transcripts in superficial adult fibrosarcoma suggests a close relationship to dermatofibrosarcoma protuberans. J Pathol 2001;194;
28 Histopathology Page 26 of Reid R, de Silva MV, Paterson L, Ryan E, Fisher C. Low-grade fibromyxoid sarcoma and hyalinizing spindle cell tumor with giant rosettes share a common t(7;16)(q34;p11) translocation. Am J Surg Pathol 2003;27; Mertens F, Fletcher CD, Antonescu CR et al. Clinicopathologic and molecular genetic characterization of low-grade fibromyxoid sarcoma, and cloning of a novel FUS/CREB3L1 fusion gene. Lab Invest 2005;85; Matsuyama A, Hisaoka M, Shimajiri S et al. Molecular detection of FUS- CREB3L2 fusion transcripts in low-grade fibromyxoid sarcoma using formalin-fixed, paraffin-embedded tissue specimens. Am J Surg Pathol 2006;30; Guillou L, Benhattar J, Gengler C et al. Translocation-positive low-grade fibromyxoid sarcoma: clinicopathologic and molecular analysis of a series expanding the morphologic spectrum and suggesting potential relationship to sclerosing epithelioid fibrosarcoma: a study from the French Sarcoma Group. Am J Surg Pathol 2007;31; Cavazzana AO, Schmidt D, Ninfo V et al. Spindle cell rhabdomyosarcoma. A prognostically favorable variant of rhabdomyosarcoma. Am J Surg Pathol 1992;16; Leuschner I. Spindle cell rhabdomyosarcoma: histologic variant of embryonal rhabdomyosarcoma with association to favorable prognosis. Curr Top Pathol 1995;89; Nascimento AF, Fletcher CD. Spindle cell rhabdomyosarcoma in adults. Am J Surg Pathol 2005;29;
29 Page 27 of 39 Histopathology 49. Mentzel T, Kuhnen C. Spindle cell rhabdomyosarcoma in adults: clinicopathological and immunohistochemical analysis of seven new cases. Virchows Arch 2006;449; Stock N, Chibon F, Binh MB et al. Adult-type rhabdomyosarcoma: analysis of 57 cases with clinicopathologic description, identification of 3 morphologic patterns and prognosis. Am J Surg Pathol 2009;33; Folpe AL, McKenney JK, Bridge JA, Weiss SW. Sclerosing rhabdomyosarcoma in adults: report of four cases of a hyalinizing, matrix-rich variant of rhabdomyosarcoma that may be confused with osteosarcoma, chondrosarcoma, or angiosarcoma. Am J Surg Pathol 2002;26; Miettinen M, Lasota J. KIT (CD117): a review on expression in normal and neoplastic tissues, and mutations and their clinicopathologic correlation. Appl Immunohistochem Mol Morphol 2005;13; Boshoff C, Schulz TF, Kennedy MM et al. Kaposi's sarcoma-associated herpesvirus infects endothelial and spindle cells. Nat Med 1995;1; Ordonez NG. Podoplanin: a novel diagnostic immunohistochemical marker. Adv Anat Pathol 2006;13; Dupin N, Fisher C, Kellam P et al. Distribution of human herpesvirus-8 latently infected cells in Kaposi's sarcoma, multicentric Castleman's disease, and primary effusion lymphoma. Proc Natl Acad Sci U S A 1999;96; Folpe AL, Veikkola T, Valtola R, Weiss SW. Vascular endothelial growth factor receptor-3 (VEGFR-3): a marker of vascular tumors with presumed lymphatic 27
30 Histopathology Page 28 of 39 differentiation, including Kaposi's sarcoma, kaposiform and Dabska-type hemangioendotheliomas, and a subset of angiosarcomas. Mod Pathol 2000;13; Chan JK, Fletcher CD, Nayler SJ, Cooper K. Follicular dendritic cell sarcoma. Clinicopathologic analysis of 17 cases suggesting a malignant potential higher than currently recognized. Cancer 1997;79; Fisher C, Magnusson B, Hardarson S, Smith ME. Myxoid variant of follicular dendritic cell sarcoma arising in the breast. Ann Diagn Pathol 1999;3; Biddle DA, Ro JY, Yoon GS et al. Extranodal follicular dendritic cell sarcoma of the head and neck region: three new cases, with a review of the literature. Mod Pathol 2002;15; Chan JKC, Fletcher CDM, Nayler SJ, Cooper K. Follicular dendritic cell sarcoma. Clinicopathologic analysis of 17 cases suggesting a malignant potential higher than currently recognized. Cancer 1997;79; Grogg KL, Macon WR, Kurtin PJ, Nascimento AG. A survey of clusterin and fascin expression in sarcomas and spindle cell neoplasms: strong clusterin immunostaining is highly specific for follicular dendritic cell tumor. Mod Pathol 2005;18; Yu H, Gibson JA, Pinkus GS, Hornick JL. Podoplanin (D2-40) is a novel marker for follicular dendritic cell tumors. Am J Clin Pathol 2007;128; Chan JKC. Proliferative lesions of follicular dendritic cells: an overview, including a detailed account of follicular dendritic cell sarcoma, a neoplasm with many faces and uncommon etiologic associations. Adv Anat Pathol 1997;6;
31 Page 29 of 39 Histopathology 64. Balercia G, Bhan AK, Dickersin GR. Sarcomatoid carcinoma: an ultrastructural study with light microscopic and immunohistochemical correlation of 10 cases from various anatomic sites. Ultrastructural Pathol 1995;19; Miettinen M, Lasota J. Gastrointestinal stromal tumors: review on morphology, molecular pathology, prognosis, and differential diagnosis. Arch Pathol Lab Med 2006;130; Andersson J, Bumming P, Meis-Kindblom JM et al. Gastrointestinal stromal tumors with KIT exon 11 deletions are associated with poor prognosis. Gastroenterology 2006;130; Lasota J, Miettinen M. KIT and PDGFRA mutations in gastrointestinal stromal tumors (GISTs). Semin Diagn Pathol 2006;23; Espinosa I, Lee CH, Kim MK et al. A novel monoclonal antibody against DOG1 is a sensitive and specific marker for gastrointestinal stromal tumors. Am J Surg Pathol 2008;32; West RB, Corless CL, Chen X et al. The novel marker, DOG1, is expressed ubiquitously in gastrointestinal stromal tumors irrespective of KIT or PDGFRA mutation status. Am J Pathol 2004;165; Miettinen M, Sobin LH, Sarlomo-Rikala M. Immunohistochemical spectrum of GISTs at different sites and their differential diagnosis with a reference to CD117 (KIT). Mod Pathol 2000;13; Fisher C. Epithelioid sarcoma of Enzinger. Adv Anat Pathol 2006;13;
32 Histopathology Page 30 of Lin L, Skacel M, Sigel JE et al. Epithelioid sarcoma: an immunohistochemical analysis evaluating the utility of cytokeratin 5/6 in distinguishing superficial epithelioid sarcoma from spindled squamous cell carcinoma. J Cutan Pathol 2003;30; Folpe AL, Chand EM, Goldblum JR, Weiss SW. Expression of Fli-1, a nuclear transcription factor, distinguishes vascular neoplasms from potential mimics. Am J Surg Pathol 2001;25; Modena P, Lualdi E, Facchinetti F et al. SMARCB1/INI1 tumor suppressor gene is frequently inactivated in epithelioid sarcomas. Cancer Res 2005;65; Orrock JM, Abbott JJ, Gibson LE, Folpe AL. INI1 and GLUT-1 expression in epithelioid sarcoma and its cutaneous neoplastic and nonneoplastic mimics. Am J Dermatopathol 2009;31; Hornick JL, Dal Cin P, Fletcher CD. Loss of INI1 expression is characteristic of both conventional and proximal-type epithelioid sarcoma. Am J Surg Pathol 2009;33; Laskin WB, Weiss SW, Bratthauer GL. Epithelioid variant of malignant peripheral nerve sheath tumor (malignant epithelioid schwannoma). Am J Surg Pathol 1991;15; Gray MH, Rosenberg AE, Dickersin GR, Bhan AK. Cytokeratin expression in epithelioid vascular neoplasms. Hum Pathol 1990;21; Meis-Kindblom JM, Kindblom LG. Angiosarcoma of soft tissue: a study of 80 cases. Am J Surg Pathol 1998;22; Billings SD, Folpe AL, Weiss SW. Epithelioid sarcoma-like hemangioendothelioma. Am J Surg Pathol 2003;27;
33 Page 31 of 39 Histopathology 81. Watabe A, Okuyama R, Hashimoto A et al. Epithelioid sarcoma-like haemangioendothelioma: a case report. Acta Derm Venereol 2009;89; Pea M, Martignoni G, Zamboni G, Bonetti F. Perivascular epithelioid cell. Am J Surg Pathol 1996;20; Folpe AL, Kwiatkowski DJ. Perivascular epithelioid cell neoplasms: pathology and pathogenesis. Hum Pathol 2010;41; Folpe AL, Mentzel T, Lehr HA, Fisher C, Balzer BL, Weiss SW. Perivascular epithelioid cell neoplasms of soft tissue and gynecologic origin: a clinicopathologic study of 26 cases and review of the literature. Am J Surg Pathol 2005;29; Harris GC, McCulloch TA, Perks G, Fisher C. Malignant perivascular epithelioid cell tumour ("PEComa") of soft tissue: a unique case. Am J Surg Pathol 2004;28; Meis-Kindblom JM. Clear cell sarcoma of tendons and aponeuroses: a historical perspective and tribute to the man behind the entity. Adv Anat Pathol 2006;13; Kosemehmetoglu K FA. Clear cell sarcoma of tendons and aponeuroses, and osteoclast-rich tumour of the gastrointestinal tract with features resembling clear cell sarcoma of soft parts: a review and update. J Clin Pathol 2010;63; Wang WL, Mayordomo E, Zhang W et al. Detection and characterization of EWSR1/ATF1 and EWSR1/CREB1 chimeric transcripts in clear cell sarcoma (melanoma of soft parts). Mod Pathol 2009;22; Rossi S, Szuhai K, Ijszenga M et al. EWSR1-CREB1 and EWSR1-ATF1 fusion genes in angiomatoid fibrous histiocytoma. Clin Cancer Res 2007;13;
Disclosures. An update on ancillary techniques in the diagnosis of soft tissue tumors. Ancillary techniques. Introduction
Disclosures An update on ancillary techniques in the diagnosis of soft tissue tumors. I have nothing to disclose. Andrew Horvai, MD, PhD Clinical Professor, Pathology Introduction Ancillary techniques
More informationDiplomate of the American Board of Pathology in Anatomic and Clinical Pathology
A 33-year-old male with a left lower leg mass. Contributed by Shaoxiong Chen, MD, PhD Assistant Professor Indiana University School of Medicine/ IU Health Partners Department of Pathology and Laboratory
More informationDisclosures. An update on ancillary techniques in the diagnosis of soft tissue tumors. Ancillary techniques. Introduction
Disclosures An update on ancillary techniques in the diagnosis of soft tissue tumors. I have nothing to disclose. Andrew Horvai, MD, PhD Clinical Professor, Pathology Introduction Ancillary techniques
More informationCutaneous Mesenchymal Neoplasms with EWSR1 Rearrangement
Cutaneous Mesenchymal Neoplasms with EWSR1 Rearrangement By Konstantinos Linos MD, FCAP, FASDP Bone, Soft Tissue and Dermatopathology Assistant Professor of Pathology Dartmouth-Hitchcock Medical Center
More informationFinancial disclosures
Cutaneous Mesenchymal Neoplasms with EWSR1 Rearrangement By Konstantinos Linos MD, FCAP, FASDP Bone, Soft Tissue and Dermatopathology Assistant Professor of Pathology Dartmouth-Hitchc Geisel School of
More informationFinancial disclosures
Mesenchymal Neoplasms with Melanocytic Differentiation By Konstantinos Linos MD, FCAP, FASDP Bone, Soft Tissue and Dermatopathology Assistant Professor of Pathology Dartmouth-Hitchcock Medical Center Geisel
More informationKlinisch belang van chromosomale translocatie detectie in sarcomen
Translocations in sarcomas Klinisch belang van chromosomale translocatie detectie in sarcomen Judith V.M.G. Bovée, M.D., Ph.D. Department of Pathology Leiden University Medical Center RNA binding DNA binding
More informationNewer soft tissue entities
Newer soft tissue entities Examples among fibroblastic tumors Turku, May 6, 2010 Markku Miettinen, M.D. AFIP, Washington, DC Fibroblastic neoplasms Solitary fibrous tumor /Hemangiopericytoma Low-grade
More informationA 25 year old female with a palpable mass in the right lower quadrant of her abdomen
May 2016 A 25 year old female with a palpable mass in the right lower quadrant of her abdomen Contributed by: Paul Ndekwe, MD, Resident Physician, Indiana University School of Department of Pathology and
More informationDiagnostic Value of Immunohistochemistry in Soft Tissue Tumors
Original Article DOI: 10.21276/APALM.1637 Diagnostic Value of Immunohistochemistry in Soft Tissue Tumors Sridevi. V*., Susruthan Muralitharan., and Thanka. J Dept of Pathology, SriMuthukumaran Medical
More informationFinancial disclosures
An update on immunohistochemical markers in mesenchymal neoplasms By Konstantinos Linos MD, FCAP, FASDP Assistant Professor of Pathology Geisel School of Medicine at Dartmouth Dartmouth-Hitchcock Medical
More information1/10/2018. Soft Tissue Tumors Showing Melanocytic Differentiation. Overview. Desmoplastic/ Spindle Cell Melanoma
2016 MFMER slide-1 2016 MFMER slide-2 2016 MFMER slide-3 Soft Tissue Tumors Showing Melanocytic Differentiation Andrew L. Folpe, M.D. Professor of Laboratory Medicine and Pathology Mayo Clinic, Rochester,
More informationCase 2. Dr. Sathima Natarajan M.D. Kaiser Permanente Medical Center Sunset
Case 2 Dr. Sathima Natarajan M.D. Kaiser Permanente Medical Center Sunset History 24 year old male presented with a 3 day history of right flank pain, sharp in nature Denies fever, chills, hematuria or
More informationTumores de células pequeñas, redondas y azules: diagnóstico diferencial cuando el tiempo apremia
Tumores de células pequeñas, redondas y azules: diagnóstico diferencial cuando el tiempo apremia Sílvia Bagué Servei de Patologia Hospital de Sant Pau Barcelona Soft tissue sarcomas Heterogeneous group
More informationContents Part I Introduction 1 General Description 2 Natural History: Importance of Size, Site, Histopathology
Contents Part I Introduction 1 General Description... 3 1.1 Introduction... 3 1.2 Incidence and Prevalence... 5 1.3 Predisposing and Genetic Factors... 8 References... 16 2 Natural History: Importance
More informationEnterprise Interest Nothing to declare
Enterprise Interest Nothing to declare Diagnoses one would not like to miss in soft tissue pathology early in your career Marta Sbaraglia, MD Department of Pathology Hospital of Treviso University of Padua
More informationUpdate on Cutaneous Mesenchymal Tumors. Thomas Brenn
Update on Cutaneous Mesenchymal Tumors Thomas Brenn Cutaneous Mesenchymal Tumours Wide morphological and biological spectrum Myofibroblastic, smooth muscle, neural, vascular, apidocytic, undifferentiated;
More informationIMMUNOHISTOCHEMISTRY IN THE DIAGNOSIS OF SOFT TISSUE TUMORS
IMMUNOHISTOCHEMISTRY IN THE DIAGNOSIS OF SOFT TISSUE TUMORS Nicolas de Saint Aubain Somerhausen Institut Jules Bordet / Hôpital Erasme nicolas.desaintaubain@synet.be ForPath 2005 1 I. Ancillary techniques
More information57th Annual HSCP Spring Symposium 4/16/2016
An Unusual Malignant Spindle Cell Lesion to Involve the Breast Erinn Downs-Kelly, D.O. Associate Professor of Pathology University of Utah & ARUP Laboratories No disclosures Case 39 y/o female with no
More informationMolecular pathology in soft tissue tumors. Sylvia Höller Pathologie
Molecular pathology in soft tissue tumors Sylvia Höller Pathologie When do we perform molecular testing? Morphology and IHC are not clearly fitting with an entity some translocations are entity specific
More informationSurgical Pathology Evening Specialty Conference USCAP 2015
Surgical Pathology Evening Specialty Conference USCAP 2015 John R. Goldblum, M.D. Chairman, Department of Pathology, Cleveland Clinic Professor of Pathology, Cleveland Clinic Lerner College of Medicine
More informationKeywords solitary fibrous tumor, dedifferentiation, dedifferentiated solitary fibrous tumor, STAT6, GRIA2, cytokeratin, rhabdomyosarcomatous
758452IJSXXX10.1177/1066896918758452International Journal of Surgical PathologyCreytens et al research-article2018 Pitfalls in Pathology Multifocal Cytokeratin Expression in a Dedifferentiated Solitary
More informationOriginal Articles. Utilization of Fluorescence In Situ Hybridization in the Diagnosis of 230 Mesenchymal Neoplasms. An Institutional Experience
Original Articles Utilization of Fluorescence In Situ Hybridization in the Diagnosis of 230 Mesenchymal Neoplasms An Institutional Experience Munir R. Tanas, MD; Brian P. Rubin, MD, PhD; Raymond R. Tubbs,
More informationACCME/Disclosures ALK FUSION-POSITIVE MESENCHYMAL TUMORS. Tumor types with ALK rearrangements. Anaplastic Lymphoma Kinase. Jason L.
Companion Meeting of the International Society of Bone and Soft Tissue Pathology The Evolving Concept of Mesenchymal Tumors ALK FUSION-POSITIVE MESENCHYMAL TUMORS Jason L. Hornick, MD, PhD March 13, 2016
More informationFluorescence In Situ Hybridization in the Diagnosis of Soft Tissue Neoplasms: A Review. Munir R. Tanas, MD and John R.
REVIEW ARTICLE Fluorescence In Situ Hybridization in the Diagnosis of Soft Tissue Neoplasms: A Review Munir R. Tanas, MD and John R. Goldblum, MD Abstract: This paper presents an overview of the role of
More informationFrom Morphology to Molecular Pathology: A Practical Approach for Cytopathologists Part 1-Cytomorphology. Songlin Zhang, MD, PhD LSUHSC-Shreveport
From Morphology to Molecular Pathology: A Practical Approach for Cytopathologists Part 1-Cytomorphology Songlin Zhang, MD, PhD LSUHSC-Shreveport I have no Conflict of Interest. FNA on Lymphoproliferative
More information59 yo male with past medical history of prostate carcinoma, presented with upper abdominal pain
December 2016 59 yo male with past medical history of prostate carcinoma, presented with upper abdominal pain Contributed by: Divya Sharma, MD. Fellow, Gastrointestinal Pathology, Department of Pathology
More informationImmunohistochemistry in Bone and Soft Tissue Tumors. Sahar Rassi Zankoul, MD
Immunohistochemistry in Bone and Soft Tissue Tumors Sahar Rassi Zankoul, MD Introduction Bone tumors represent a wide variety of tumors of various origins and malignant potentials. These different tumor
More informationImmunohistochemical Staining for Claudin-1 Can Help Distinguish Meningiomas From Histologic Mimics
Anatomic Pathology / CLAUDIN-1 IN MENINGIOMAS Immunohistochemical Staining for Claudin-1 Can Help Distinguish Meningiomas From Histologic Mimics Hejin P. Hahn, MD, PhD, Elizabeth A. Bundock, MD, PhD, and
More information5/10. Pathology Soft tissue tumors. Farah Bhani. Mohammed Alorjani
5/10 Pathology Soft tissue tumors Mohammed Alorjani Farah Bhani Slides are included in this sheet. Objectives: Soft tissue tumors 1. Describe soft tissue tumors. 2. Understand the classification of soft
More informationSpindle Cell Lesions Of The Breast. Emad Rakha Professor of Breast Pathology and Consultant Pathologist
Spindle Cell Lesions Of The Breast Emad Rakha Professor of Breast Pathology and Consultant Pathologist * SCLs comprise a wide spectrum of diseases, ranging from reactive processes to aggressive malignant
More informationShintaro Sugita *, Hiroko Asanuma and Tadashi Hasegawa
Sugita et al. Diagnostic Pathology (2016) 11:37 DOI 10.1186/s13000-016-0486-2 RESEARCH Open Access Diagnostic use of fluorescence in situ hybridization in expert review in a phase 2 study of trabectedin
More informationAffiliazione autori0. Riccardo Ricci Journal Club GIPAD, settore GIST Anatomia Patologica, Università Cattolica, Roma
GIST Manifesting as a Retroperitoneal Tumor: Clinicopathologic Immunohistochemical, and Molecular Genetic Study of 112 Cases American Journal of Surgical Pathology, 2017, 41:577-585 Miettinen M*; Felisiak-Golabek
More informationMolecular Diagnosis of Soft Tissue Tumors: Avoid Pitfalls
Molecular Diagnosis of Soft Tissue Tumors: Avoid Pitfalls Cristina Antonescu, MD Department of Pathology Memorial Sloan-Kettering Cancer Center, New York Overview I. When should we rely on the help of
More informationEvening Specialty Conference Bone and Soft Tissue Pathology. Diagnostic pitfalls in bone and soft tissue pathology
Evening Specialty Conference Bone and Soft Tissue Pathology. Case 1 Elizabeth G Demicco, MD, PhD Mount Sinai Hospital, New York Disclosure of Relevant Financial Relationships USCAP requires that all planners
More information3/27/2017. Disclosure of Relevant Financial Relationships
Ophthalmic Pathology Evening Specialty Conference USCAP 2017 5 th March, 2017 Mukul K. Divatia, MD Assistant Professor Department of Pathology & Genomic Medicine Weill Cornell Medical College Houston Methodist
More informationNo financial or other disclosures
Case 2014-5 Esther N. Bit-Ivan, DO Northwestern University Jason Wang, MD Jason Park, MD Korgun Koral, MD Children s Medical Center Charles Timmons, MD Veena Rajaram, MD No financial or other disclosures
More informationUSCAP 2011: ASDP companion meeting. Steven D. Billings 1
USCAP 2011: ASDP companion meeting. Steven D. Billings (billins@ccf.org) 1 Spindle cell tumors that make you say, Oh $*&%! This lecture will focus on examples of cutaneous tumors that present particular
More informationClassification (1) Classification (3) Classification (2) Spindle cell lesions. Spindle cell lesions of bladder (Mills et al.
Non-epithelial tumours and nonepithelial tumour-like lesions of the bladder Dr Jonathan H Shanks The Christie NHS Foundation Trust, Manchester, UK Classification (1) Myofibroblastic proliferations and
More information3/24/2017 DENDRITIC CELL NEOPLASMS: HISTOLOGY, IMMUNOHISTOCHEMISTRY, AND MOLECULAR GENETICS. Disclosure of Relevant Financial Relationships
DENDRITIC CELL NEOPLASMS: HISTOLOGY, IMMUNOHISTOCHEMISTRY, AND MOLECULAR GENETICS Jason L. Hornick, M.D., Ph.D. Director of Surgical Pathology and Immunohistochemistry Brigham and Women s Hospital Professor
More informationCase 1. Disclosure. Imaging. Clinical history 5/10/2016. USCAP 2016 Annual Meeting Evening Specialty Conference Bone and Soft tissue Pathology
Disclosure Dr. Agaram has nothing to disclose Case 1 Narsi Agaram, MBBS USCAP 2016 Annual Meeting Evening Specialty Conference Bone and Soft tissue Pathology Clinical history Imaging 1998 A three month
More informationPathology of Sarcoma ELEANOR CHEN, MD, PHD, ASSISTANT PROFESSOR DEPARTMENT OF PATHOLOGY UNIVERSITY OF WASHINGTON
Pathology of Sarcoma ELEANOR CHEN, MD, PHD, ASSISTANT PROFESSOR DEPARTMENT OF PATHOLOGY UNIVERSITY OF WASHINGTON Presentation outline Background and epidemiology of sarcomas Sarcoma classification Sarcoma
More informationSelected Pseudomalignant Soft Tissue Tumors of the Skin and Subcutis
Selected Pseudomalignant Soft Tissue Tumors of the Skin and Subcutis Andrew L. Folpe, M.D. Professor of Laboratory Medicine and Pathology Mayo Clinic, Rochester, MN folpe.andrew@mayo.edu 2016 MFMER slide-1
More informationLung Tumor Cases: Common Problems and Helpful Hints
Lung Tumor Cases: Common Problems and Helpful Hints Brandon T. Larsen, MD, PhD Senior Associate Consultant Department of Laboratory Medicine and Pathology Mayo Clinic Arizona Arizona Society of Pathologists
More informationBreast - ductal carcinoma CK7 ER PR GATA3 Mammaglobin (50-70%) GCDFP-15 (50-70%) E-cadherin HMWCK CK20 PAX2 ER/PR/HER2 on all newly diagnosed cases
Adrenal cortical carcinoma Inhibin Synap Melan-A Calretinin Vimentin Chromogr CK7 CK20 Breast - ductal carcinoma CK7 ER PR GATA3 Mammaglobin (50-70%) GCDFP-15 (50-70%) E-cadherin HMWCK CK20 PAX2 ER/PR/HER2
More informationCASE REPORT Benign epithelioid peripheral nerve sheath tumour resembling schwannoma
Malaysian J Pathol 2014; 36(3) : 217 221 CASE REPORT Benign epithelioid peripheral nerve sheath tumour resembling schwannoma Thejasvi KRISHNAMURTHY MD and SR NIVEDITHA MD, DNB Department of Pathology,
More informationأملس عضلي غرن = Leiomyosarcoma. Leiomyosarcoma 1 / 5
Leiomyosarcoma 1 / 5 EPIDEMIOLOGY Exact incidence is unknown, but older studies suggest that leiomyosarcomas comprise approximately 3 percent of soft-tissue sarcomas. Superficial leiomyosarcoma occurs
More informationSOFT TISSUE TUMOR PATHOLOGY: AN UPDATE
SOFT TISSUE TUMOR PATHOLOGY: AN UPDATE Jason L. Hornick, MD, PhD July 18, 2013 Department of Pathology Brigham and Women s Hospital Harvard Medical School Boston, MA, USA I have no disclosures. New Soft
More informationCase: The patient is a 24 year- old female who was found to have multiple mural nodules within the antrum. Solid and cystic components were noted on
Case: The patient is a 24 year- old female who was found to have multiple mural nodules within the antrum. Solid and cystic components were noted on imaging. There is no significant past medical history.
More informationESS: Pathologic Insights
GEIS XVI INTERNATIONAL SYMPOSIUM Seville 4th October 2018 ESS: Pathologic Insights Sílvia Bagué The Royal Marsden Hospital London (United Kingdom) I have no conflicts of interest Endometrial stromal sarcoma
More informationRhabdomyomas and Rhabdomyosarcomas (RMS) David M. Parham, MD Chief of Anatomic Pathology
Rhabdomyomas and Rhabdomyosarcomas (RMS) David M. Parham, MD Chief of Anatomic Pathology Tumors of skeletal muscle: Rhabdomyomas and rhabdomyosarcomas Embryonal muscle 2 3 4 5 6 7 8 Rhabdomyoma Benign
More informationThe Genetics of Myoepithelial Tumors: salivary glands, soft tissue and bone
The Genetics of Myoepithelial Tumors: salivary glands, soft tissue and bone Cristina Antonescu, MD Memorial Sloan-Kettering Cancer Center, New York Nothing to declare Disclosure Spectrum of Myoepithelial
More informationPathology Mystery and Surprise
Pathology Mystery and Surprise Tim Smith, MD Director Anatomic Pathology Medical University of South Carolina Disclosures No conflicts to declare Some problem cases Kidney tumor Scalp tumor Bladder tumor
More informationKhin Thway, Jayson Wang, Taka Mubako, and Cyril Fisher. 1. Introduction
Sarcoma, Article ID 686902, 7 pages http://dx.doi.org/10.1155/2014/686902 Research Article Histopathological Diagnostic Discrepancies in Soft Tissue Tumours Referred to a Specialist Centre: Reassessment
More informationSlide Seminar Spanish Society of Pathology
Slide Seminar Spanish Society of Pathology John R. Goldblum, M.D. Chairman, Department of Anatomic Pathology Cleveland Clinic Professor of Pathology Cleveland Clinic Lerner College of Medicine 1921 Original
More informationSpecial slide seminar
Special slide seminar Tomáš Rozkoš The Fingerland Department of Pathology Charles University Medical Faculty and Faculty Hospital in Hradec Králové Czech Republic Case history, 33 years old resistance
More informationBiopsy Interpretation of Spindle cell proliferations of the Serosa
Biopsy Interpretation of Spindle cell proliferations of the Serosa Richard Attanoos, Cardiff. U.K. Disclosure of Relevant Financial Relationships USCAP requires that all planners (Education Committee)
More informationPart 1. Slides 1-38, Rita Alaggio Soft tissue tumors Trondheim 14. mars 2013
Part 1 Slides 1-38, Rita Alaggio Soft tissue tumors Trondheim 14. mars 2013 Pediatric Pathology Soft Tissue Tumors AN UPDATE Rita Alaggio Azienda Ospedaliera Università di Padova Soft Tissue Tumors More
More informationThe Impact of Advances in Molecular Genetic Pathology on the. Classification, Diagnosis and Treatment of Selected Soft Tissue
The Impact of Advances in Molecular Genetic Pathology on the Classification, Diagnosis and Treatment of Selected Soft Tissue Tumors of the Head and Neck Joaquín J. García MD and Andrew L. Folpe MD Department
More informationThe Relevance of Cytologic Atypia in Cutaneous Neural Tumors
The Relevance of Cytologic Atypia in Cutaneous Neural Tumors Recent Findings - New Developments New Problems Zsolt B. Argenyi, M.D. Professor of Pathology & Dermatology Director of Dermatopathology Department
More informationMayo Medical Laboratories
Mayo Medical Laboratories Virtual Lectures 2014 MFMER 2016 MFMER slide-1 Virtual Lectures Planning Committee Disclosure Summary As a provider accredited by ACCME, College of Medicine, Mayo Clinic (Mayo
More informationSynovial Sarcoma with Massive Myxoid Feature
The Korean Journal of Pathology 2005; 39: 273-7 Synovial Sarcoma with Massive Myxoid Feature - Case Report - Joon Hyuk Choi Young Ran Shim Young Kyung ae Mi Jin Kim Duk Seop Shin 1 Kil Ho Cho 2 Departments
More informationConceptual Evolution of Soft Tissue Tumors Classification
Conceptual Evolution of Soft Tissue Tumors Classification Angelo P. Dei Tos M.D. Departments of Pathology & Oncology Treviso, Italy How WHO classification was reshaped Pathologists and Cytogeneticists
More informationDisclosure of Relevant Financial Relationships
Ewing and Ewing like sarcomas Using Genetic Signatures in Refining Small Blue Round Cell Tumor Classification Cristina Antonescu, MD Department of Pathology Disclosure of Relevant Financial Relationships
More informationMesothelioma: diagnostic challenges from a pathological perspective. Naseema Vorajee August 2016
Mesothelioma: diagnostic challenges from a pathological perspective Naseema Vorajee August 2016 Naseema.vorajee@nhls.ac.za Pleural diseases (whether neoplastic, reactive or infective) may have similar
More informationSchedule of Accreditation issued by United Kingdom Accreditation Service 2 Pine Trees, Chertsey Lane, Staines-upon-Thames, TW18 3HR, UK
2 Pine Trees, Chertsey Lane, Staines-upon-Thames, TW18 3HR, UK Royal National Orthopaedic Hospital NHS Trust Brockley Hill Stanmore Middlesex HA7 4LP Contact: Professor Adrienne Flanagan Tel: +44 (0)20
More informationGUT-C 11/30/2017. Debasmita Das, M.D. PGY-1 Danbury Hospital
GUT-C 11/30/2017 Debasmita Das, M.D. PGY-1 Danbury Hospital CLINICAL SUMMARY 8/2017 59 year old female Presented to the ED with 1 month history of general malaise, fever and weight loss PMH: Significant
More informationUpdate On Lipomatous Tumors: Old Standbys and New Concepts
Update On Lipomatous Tumors: Old Standbys and New Concepts John R. Goldblum, M.D. Chairman, Department of Anatomic Pathology Cleveland Clinic Professor of Pathology Cleveland Clinic Lerner College of Medicine
More informationMojca Velikonja Jože Pižem
Mojca Velikonja Jože Pižem An 81-year old woman presented with an exophytic, wart-like skin lesion on her neck that she had observed for one year. Cryotherapy had been applied twice, but proved unsuccessful.
More informationEvaluating and Reporting Gastrointestinal Stromal Tumors after Imatinib Mesylate Treatment
The Open Pathology Journal, 2009, 3, 53-57 53 Open Access Evaluating and Reporting Gastrointestinal Stromal Tumors after Imatinib Mesylate Treatment Katie L. Dennis * and Ivan Damjanov Department of Pathology
More informationHOW MAY THE CLASSIFICATION OF SOFT TISSUE TUMORS EVOLVE?
Spanish Society of Pathology Zaragoza, May 2011 ARTHUR PURDY STOUT SYMPOSIUM HOW MAY THE CLASSIFICATION OF SOFT TISSUE TUMORS EVOLVE? Christopher D.M. Fletcher, M.D., FRCPath Brigham and Women s Hospital
More informationLOOK-ALIKES IN SPINDLE AND EPITHELIOID TUMORS: Immunohistochemistry. Cytogenetics Flow cytometry Molecular diagnostics
LOOK-ALIKES IN SPINDLE AND EPITHELIOID TUMORS: Ultrastructural value and pitfalls in diagnosis Guillermo A Herrera Department of Pathology and Translational Pathobiology Louisiana State University Health
More informationGastrointestinal stromal tumor
Gastrointestinal stromal tumor 영남의대병리학교실 최준혁 Classification of gastrointestinal mesenchymal tumor Gastrointestinal stromal tumor(gist) Smooth muscle tumors : leiomyoma, leiomyosarcoma Neurogenic tumors
More informationDesmoplastic Melanoma R/O BCC. Clinical Information. 74 y.o. man with lesion on left side of neck r/o BCC
R/O BCC Sabine Kohler, M.D. Professor of Pathology and Dermatology Dermatopathology Service Stanford University School of Medicine Clinical Information 74 y.o. man with lesion on left side of neck r/o
More informationSoft Tissue Perineurioma
The Korean Journal of Pathology 2009; 43: 266-70 DOI: 10.4132/KoreanJPathol.2009.43.3.266 Soft Tissue Perineurioma - A Case Report - Jun Mo Kim Joon Hyuk Choi Department of Pathology, Yeungnam University
More informationMimics of Sarcoma. I have no conflict of interest to declare
Maastricht 2018 Mimics of Sarcoma Cyril Fisher MA MD DSc FRCPath Consultant Pathologist, Royal Orthopaedic Hospital, Birmingham, UK Emeritus Professor of Tumour Pathology Institute of Cancer Research,
More informationNEW IHC A n t i b o d i e s
NEW IHC Antibodies TABLE OF CONTENTS NEW IHC ANTIBODIES from Cell Marque CITED1 (5H6).... 1 Claudin 7 (5D10F3).... 1 GATA1 (4F5).... 1 Transgelin (2A10C2).... 1 NEW IHC ANTIBODIES using RabMAb Technology
More informationMesothelioma Pathobasic. Lukas Bubendorf Pathology
Mesothelioma Pathobasic Lukas Bubendorf Pathology Mechanisms of Asbestos Carcinogenesis in Mesothelioma Asprin High-mobility group protein B1 master switch HMGB1 Initiation/ perpetuation of inflamm. response
More informationCheryl M. Coffin, M.D. Goodpasture Professor of Pathology, Microbiology, and Immunology Vanderbilt University Nashville, TN, USA
Cutaneous Mesenchymal Tumors in Childhood Cheryl M. Coffin, M.D. Goodpasture Professor of Pathology, Microbiology, and Immunology Vanderbilt University Nashville, TN, USA I. Introduction Cutaneous tumors
More informationImmunohistochemical Staining for KIT (CD117) in Soft Tissue Sarcomas Is Very Limited in Distribution
Anatomic Pathology / KIT IN SOFT TISSUE SARCOMAS Immunohistochemical Staining for KIT (CD117) in Soft Tissue Sarcomas Is Very Limited in Distribution Jason L. Hornick, MD, PhD, and Christopher D.M. Fletcher,
More informationCellular Neurothekeoma
Cellular Neurothekeoma Scott W Binder, MD Pritzker Professor of Pathology & Dermatology Sr. Vice Chair Director, Pathology Clinical Services Chief, Dermatopathology Geffen/UCLA School of Medicine Clinical
More informationFollicular dendritic cell sarcoma of inguinal lymph node A case report
Malaysian J Pathol 2008; 30(2) : 115 119 CASE REPORT Follicular dendritic cell sarcoma of inguinal lymph node A case report Jayalakshmi PAILOOR, MPath, FRCPath, Krishnan R IYENGAR, MD, DNB, CHAN KS, MPath*
More informationHemangioendothelioma with a Prominent Lymphoid Infiltrate Mimicking Follicular Dendritic Cell Tumor: Report of a Case
Journal of Cancer Research Updates, 2013, 2, 135-139 135 Hemangioendothelioma with a Prominent Lymphoid Infiltrate Mimicking Follicular Dendritic Cell Tumor: Report of a Case Justin Kerstetter 1, Mia Perez
More informationPROBLEMS OF PROGNOSTICATION IN SOFT TISSUE TUMOURS. Christopher D.M. Fletcher Brigham and Women s Hospital and Harvard Medical School Boston, MA
PROBLEMS OF PROGNOSTICATION IN SOFT TISSUE TUMOURS Christopher D.M. Fletcher Brigham and Women s Hospital and Harvard Medical School Boston, MA Dr. Fletcher has no conflict of interest or disclosures to
More informationCase Report Intraneural malignant perineurioma: a case report and review of literature
Int J Clin Exp Pathol 2014;7(7):4503-4507 www.ijcep.com /ISSN:1936-2625/IJCEP0000923 Case Report Intraneural malignant perineurioma: a case report and review of literature Yong Huang 1, Hongwei Li 1, Zhengwen
More informationSlide seminar: Soft tissue and bone pathology
Slide seminar: Soft tissue and bone pathology Unusual tumors of bone and soft tissue or unusual presentations of common ones Gunhild Mechtersheimer Institute of Pathology, Heidelberg/DE (Sylvia Höller,
More information21/07/2017. Hobnail endothelial cells are not the same as epithelioid endothelial cells
UPDATE IN CUTANEOUS VASCULAR S DERMATOPATHOLOGY SESSION BELFAST PATHOLOGY JUNE 21/2017 Dr E Calonje St John s Institute of Dermatology, London, United Kingdom THE FAMILY OF VASCULAR S WITH EPITHELIOID
More informationSelf assessment case. Dr Saleem Taibjee Dorset County Hospital, Dorchester
Self assessment case Dr Saleem Taibjee saleemtaibjee@gmail.com Dorset County Hospital, Dorchester Clinical details 34-year-old man: Shave excision Skin tag / papilloma left thigh The best diagnosis is:
More informationOriginal Article Differential diagnosis of sarcomatoid mesothelioma from true sarcoma and sarcomatoid carcinoma using immunohistochemistry
Pathology International 2008; 58: 75 83 doi:10.1111/j.1440-1827.2007.02193.x Original Article Differential diagnosis of sarcomatoid mesothelioma from true sarcoma and sarcomatoid carcinoma using immunohistochemistry
More informationMalignant Peripheral Nerve Sheath Tumor
C H A P T E R 120 Malignant Peripheral Nerve Sheath Tumor Currently, malignant peripheral nerve sheath tumor (MPNST) is the most commonly used generic name for the neoplasms known in the past as neurosarcoma,
More informationI have nothing to disclose
A 47 year old female with multiple lung nodules Disclosure of Relevant Financial Relationships Tamar Giorgadze, MD, PhD Professor of Pathology Medical College of Wisconsin Milwaukee, Wisconsin USCAP requires
More informationUpdate on Sarcomas of the Head and Neck. Kevin Harrington
Update on Sarcomas of the Head and Neck Kevin Harrington Overview Classification and incidence of sarcomas Clinical presentation Challenges to treatment Management approaches Prognostic factors Radiation-induced
More informationAspen conference on pediatric disease. July through August Bone and Soft Tissue Update. David M. Parham, MD. Rhabdomyoma and rhabdomyosarcoma
Aspen conference on pediatric disease July through August 2014 Bone and Soft Tissue Update David M. Parham, MD Rhabdomyoma and rhabdomyosarcoma Embryonic rhabdomyogenesis is a highly conserved process
More informationDisclosure. Relevant Financial Relationship(s) None. Off Label Usage None MFMER slide-1
Disclosure Relevant Financial Relationship(s) None Off Label Usage None 2013 MFMER slide-1 Case Presentation A 43 year old male, with partial nephrectomy for a right kidney mass 2013 MFMER slide-2 2013
More informationSayed A. S. Pathology Department, Faculty of Medicine, Al-Azhar University, Cairo
Role of expression of P53, Cyclin D1 and Epidermal growth factor receptor (EGFR) in some benign, intermediate and malignant spindle cell soft tissue tumors Sayed A. S. Pathology Department, Faculty of
More information4/12/2018. MUSC Pathology Symposium Kiawah Island April 18, Jesse K. McKenney, MD
MUSC Pathology Symposium Kiawah Island April 18, 2018 Jesse K. McKenney, MD 1 Urothelial Carcinoma with Alternative Differentiation 2 Urothelial Carcinoma with Alternative Differentiation Recognition as
More informationPrognostic Significance of Grading and Staging Systems using MIB-1 Score in Adult Patients with Soft Tissue Sarcoma of the Extremities and Trunk
843 Prognostic Significance of Grading and Staging Systems using MIB-1 Score in Adult Patients with Soft Tissue Sarcoma of the Extremities and Trunk Tadashi Hasegawa, M.D. 1 Seiichiro Yamamoto, Ph.D. 2
More informationAtypical Palisaded Myofibroblastoma of Lymph Node: Report of a rare case.
ISPUB.COM The Internet Journal of Pathology Volume 10 Number 1 Atypical Palisaded Myofibroblastoma of Lymph Node: Report of a rare case. V Kinnera, R Nandyala, M Yootla, K Mandyam Citation V Kinnera, R
More informationCase Presentation. Maha Akkawi, MD, Fatima Obeidat, MD, Tariq Aladily, MD. Department of Pathology Jordan University Hospital Amman, Jordan
Case Presentation Maha Akkawi, MD, Fatima Obeidat, MD, Tariq Aladily, MD Department of Pathology Jordan University Hospital Amman, Jordan The 25th Annual Congress of the ADIAP The 8/11/2013 1 5th International
More informationApplications of IHC. Determination of the primary site in metastatic tumors of unknown origin
Applications of IHC Determination of the primary site in metastatic tumors of unknown origin Classification of tumors that appear 'undifferentiated' by standard light microscopy Precise classification
More information