Abstract
Immunohistochemistry is a powerful adjunctive technique for the pathologic diagnosis of soft tissue and bone tumors, although some tumors still lack of specific markers. This chapter includes the questions about the immunohistochemical markers for normal soft tissue and bone, soft tissue and bone tumors, and their utility for differentiation. The questions are answered in the form of tables. The photos of selected markers are also included. New markers such as claudin-5, ERG, GAP43, INI1, MDM2, MUC4, NKX2.2, NY-ESO-1, SATB2, SOX9, SOX10, STAT6, as well as other commonly used markers are discussed.
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Keywords
- Adamantinoma
- Aggressive angiomyxoma
- Alveolar soft part sarcoma
- Angiomatoid fibrous histiocytoma
- Angiosarcoma
- Atypical fibroxanthoma
- Chordoma
- Clear cell sarcoma of soft parts
- Dermatofibrosarcoma protuberans
- Desmoplastic small round cell tumor
- Epithelioid sarcoma
- Ewing sarcoma
- Fibromatosis
- Glomangiopericytoma
- Glomus tumors
- Granular cell tumor
- Hemangioendothelioma
- Hemangiopericytoma
- Inflammatory myofibroblastic tumor
- Kaposi sarcoma
- Langerhans cell histiocytosis
- Leiomyosarcoma
- Liposarcoma
- Low-grade myofibroblastic sarcoma
- Low grade fibromyxoid sarcoma
- Malignant extrarenal rhabdoid tumor
- Malignant melanotic schwannian tumor
- Mammary-type myofibroblastoma myofibroma
- Mesenchymal chondrosarcoma
- Myoepithelial tumors
- Myxofibrosarcoma
- Neurofibroma
- Neurothekeomas
- Neuroblastoma
- Nodular fasciitis
- Notochord
- Osteosarcoma
- Ossifying fibromyxoid tumor of soft parts
- Perineurioma
- Perivascular epithelioid cell neoplasms
- Phosphaturic mesenchymal tumor
- Pleomorphic hyalinizing angiectatic tumor
- Primitive neuroectodermal tumor
- Reticulohistiocytoma
- Rhabdomyosarcoma
- Schwannoma
- Solitary fibrous tumor
- Spindle cell hemangioma
- Synovial sarcoma
- Undifferentiated pleomorphic sarcoma
- β-catenin
- Brachyury
- Calponin
- CD1a
- CD31
- CD34
- CD99
- Chromogranin A
- Claudin-1
- CDK4
- Desmin
- ERG
- FLI1
- GLUT1
- h-Caldesmon
- HHV8 LANA
- HMB-45
- INI1
- MDM2
- Melan A
- MITF
- MUC4
- myoD1
- Myogenin
- NB84
- NKX2.2
- NY-ESO-1
- S100
- SATB2
- SOX9
- SOX10
- STAT6
- TFE3
- TLE1
- Type IV collagen
- Vimentin
- WT-1
Frequently Asked Questions
-
29.1.
Summary of applications and limitations of useful markers (Table 29.1)
Table 29.1 Summary of applications and limitations of useful markers -
29.2.
Markers positive for normal soft tissue and bone (Table 29.2)
Table 29.2 Markers positive for normal soft tissue and bone
Adipocytic Tumors
-
29.3.
Markers for spindle cell lipoma/pleomorphic lipoma (Table 29.3)
Table 29.3 Markers for spindle cell lipoma/pleomorphic lipoma -
29.4.
Markers for well-differentiated liposarcoma/dedifferentiated liposarcoma (Table 29.4)
Table 29.4 Markers for well-differentiated liposarcoma/dedifferentiated liposarcoma -
29.5.
Markers for myxoid/round cell liposarcoma (Table 29.5)
Table 29.5 Markers for myxoid/round cell liposarcoma
Fibroblastic and Fibrohistiocytic Tumors
-
29.6.
Markers for nodular fasciitis (Table 29.6)
Table 29.6 Markers for nodular fasciitis -
29.7.
Markers for palmar and plantar (superficial) fibromatosis (Table 29.7)
Table 29.7 Markers for palmar and plantar (superficial) fibromatosis -
29.8.
Markers for deep fibromatosis (Table 29.8)
Table 29.8 Markers for deep fibromatosis -
29.9.
Markers for fibrous hamartoma of infancy (Table 29.9)
Table 29.9 Markers for fibrous hamartoma of infancy -
29.10.
Markers for inflammatory myofibroblastic tumor/inflammatory fibrosarcoma (Table 29.10)
Table 29.10 Markers for Inflammatory myofibroblastic tumor/inflammatory fibrosarcoma -
29.11.
Markers of myofibroma/myofibromatosis (Table 29.11)
Table 29.11 Markers of myofibroma/myofibromatosis -
29.12.
Markers for angiomyofibroblastoma (Table 29.12)
Table 29.12 Markers for angiomyofibroblastoma -
29.13.
Markers for cellular angiofibroma (Table 29.13)
Table 29.13 Markers for cellular angiofibroma -
29.14.
Markers of mammary-type myofibroblastoma (Table 29.14)
Table 29.14 Markers of mammary-type myofibroblastoma -
29.15.
Markers for myxoinflammatory fibroblastic sarcoma (Table 29.15)
Table 29.15 Markers for myxoinflammatory fibroblastic sarcoma -
29.16.
Markers for low-grade myofibroblastic sarcoma (Table 29.16)
Table 29.16 Markers for low-grade myofibroblastic sarcoma -
29.17.
Markers for low-grade fibromyxoid sarcoma including spindle cell tumor with giant rosettes (Table 29.17)
Table 29.17 Markers for low-grade fibromyxoid sarcoma/ spindle cell tumor with giant rosettes -
29.18.
Markers for myxofibrosarcoma (Table 29.18)
Table 29.18 Markers for myxofibrosarcoma
Fibrohistiocytic Tumors
-
29.19.
Markers for benign fibrous histiocytoma (Table 29.19)
Table 29.19 Markers for benign fibrous histiocytoma -
29.20.
Markers for juvenile xanthogranuloma and reticulohistiocytoma (Table 29.20)
Table 29.20 Markers for juvenile xanthogranuloma and reticulohistiocytoma -
29.21.
Markers for atypical fibroxanthoma (Table 29.21)
Table 29.21 Markers for atypical fibroxanthoma -
29.22.
Markers for dermatofibrosarcoma protuberans/giant cell fibroblastoma (Table 29.22)
Table 29.22 Markers for dermatofibrosarcoma protuberans/giant cell fibroblastoma -
29.23.
Markers for angiomatoid fibrous histiocytoma (Table 29.23)
Table 29.23 Markers for angiomatoid (malignant) fibrous histiocytoma -
29.24.
Markers for plexiform fibrohistiocytic tumor (Table 29.24)
Table 29.24 Markers for plexiform fibrohistiocytic tumor -
29.25.
Markers for giant cell tumor of soft tissue (Table 29.25)
Table 29.25 Markers for giant cell tumor of soft tissue -
29.26.
Markers for undifferentiated pleomorphic sarcoma (pleomorphic malignant fibrous histiocytoma) (Table 29.26)
Table 29.26 Markers for undifferentiated pleomorphic sarcoma (pleomorphic malignant fibrous histiocytoma)
Smooth Muscle Tumors
-
29.27.
Markers for leiomyoma and leiomyosarcoma (Table 29.27)
Table 29.27 Markers for leiomyoma and leiomyosarcoma Fig. 29.1 
(a) Leiomyosarcoma shows positive staining for desmin, (b) Leiomyosarcoma shows positive staining for h-caldesmon
-
29.28.
Markers for EBV-related leiomyosarcoma (Table 29.28)
Table 29.28 Markers for EBV-associated leiomyosarcoma
Skeletal Muscle Tumors
-
29.29.
Markers for rhabdomyoma (Table 29.29)
Table 29.29 Markers for rhabdomyoma -
29.30.
Markers for rhabdomyosarcoma (Table 29.30)
Table 29.30 Markers for rhabdomyosarcoma Fig. 29.2 
(a) Rhabdomyosarcoma shows positive staining for MyoD1, (b) Rhabdomyosarcoma shows positive staining for myogenin
Tumors of Perivascular Cells
-
29.31.
Markers for hemangiopericytoma (HPC)/solitary fibrous tumor (SFT) of soft tissue (Table 29.31)
Table 29.31 Markers for hemangiopericytoma (HPC)/solitary fibrous tumor (SFT) of soft tissue Fig. 29.3 
Solitary fibrous tumor shows positive staining for CD34
-
29.32.
Markers for myopericytoma family of tumors (infantile myofibromatosis, solitary myofibroma, infantile hemangiopericytoma, myopericytoma, glomangiopericytoma) (Table 29.32)
Table 29.32 Markers for myopericytoma family of tumors (infantile myofibromatosis, solitary myofibroma, infantile hemangiopericytoma myopericytoma, glomangiopericytoma) -
29.33.
Markers for glomus tumor (Table 29.33)
Table 29.33 Markers for glomus tumor Fig. 29.4 
(a) Glomus tumor on H&E section, (b) Glomus tumor shows positive staining for SMA
Vascular Tumors
-
29.34.
Markers for kaposiform hemangioendothelioma (Table 29.34)
Table 29.34 Markers for kaposiform hemangioendothelioma -
29.35.
Markers for hemangioma (Table 29.35)
Table 29.35 Markers for hemangioma -
29.36.
Markers for Dabska-type and retiform hemangioendothelioma (Table 29.36)
Table 29.36 Markers for Dabska-type and retiform hemangioendothelioma -
29.37.
Markers for epithelioid hemangioendothelioma (Table 29.37)
Table 29.37 Markers for epithelioid hemangioendothelioma -
29.38.
Markers for angiosarcoma (Table 29.38)
Table 29.38 Markers for angiosarcoma Fig. 29.5 
(a) Angiosarcoma shows positive staining for ERG, (b) Angiosarcoma shows positive staining for CD31
-
29.39.
Markers for Kaposi sarcoma (Table 29.39)
Table 29.39 Markers for Kaposi sarcoma -
29.40.
Markers for lymphatic tumors (Table 29.40)
Table 29.40 Markers for lymphatic tumors
Nerve Sheath and Neuroectodermal Tumors
-
29.41.
Markers for neurofibroma (Table 29.41)
Table 29.41 Markers for neurofibroma -
29.42.
Markers for schwannoma/nerve sheath myxoma (Table 29.42)
Table 29.42 Markers for schwannoma/nerve sheath myxoma Fig. 29.6 
Schwannoma shows positive staining for S100
-
29.43.
Markers for psammomatous melanotic schwannoma/malignant melanotic schwannian tumor (Table 29.43)
Table 29.43 Markers for psammomatous melanotic schwannoma/melanotic schwannian tumor -
29.44.
Markers for malignant peripheral nerve sheath tumor (MPNST) (Table 29.44)
Table 29.44 Markers for malignant peripheral nerve sheath tumor (MPNST) -
29.45.
Markers for granular cell tumor (Table 29.45)
Table 29.45 Markers for granular cell tumor -
29.46.
Markers for neurothekeomas (Table 29.46)
Table 29.46 Markers for cellular neurothekeomas (fibrohistiocytic tumor) -
29.47.
Markers for perineurioma (Table 29.47)
Table 29.47 Markers for perineurioma -
29.48.
Markers for neuroblastoma (Table 29.48)
Table 29.48 Markers for neuroblastoma Fig. 29.7 
(a) Neuroblastoma shows positive staining for CD56, (b) Neuroblastoma shows positive staining for synaptophysin
-
29.49.
Markers for clear cell sarcoma of soft parts (Table 29.49)
Table 29.49 Markers for clear cell sarcoma of soft parts
Tumors of Uncertain Differentiation
-
29.50.
Markers for myxoma (Table 29.50)
Table 29.50 Markers for myxoma -
29.51.
Markers for aggressive angiomyxoma (Table 29.51)
Table 29.51 Markers for aggressive angiomyxoma -
29.52.
Markers for ossifying fibromyxoid tumor of soft parts (Table 29.52)
Table 29.52 Markers for ossifying fibromyxoid tumor of soft parts -
29.53.
Markers for myoepithelial tumors (mixed tumor/myoepithelioma/parachordoma) (Table 29.53)
Table 29.53 Markers for mixed tumor/myoepithelioma/parachordoma(myoepithelial tumors) -
29.54.
Markers for pleomorphic hyalinizing angiectatic tumor (Table 29.54)
Table 29.54 Markers for pleomorphic hyalinizing angiectatic tumor -
29.55.
Markers for phosphaturic mesenchymal tumor (Table 29.55)
Table 29.55 Markers for phosphaturic mesenchymal tumor -
29.56.
Markers for perivascular epithelioid cell neoplasms (angiomyolipoma of the kidney or other organs, clear cell sugar tumor of the lung, lymphangioleiomyomatosis, clear cell myomelanocytic tumor of the falciform ligament/ligamentum teres) (Table 29.56)
Table 29.56 Markers for perivascular epithelioid cell family of tumors (PEComas) (angiomyolipoma of the kidney or other organs, clear cell sugar tumor of the lung, lymphangioleiomyomatosis, clear cell myomelanocytic tumor of the falciform ligament/ligamentum teres) -
29.57.
Markers for epithelioid sarcoma (Table 29.57)
Table 29.57 Markers for epithelioid sarcoma Fig. 29.8 
(a) Epithelioid sarcoma on H&E section, (b) Epithelioid sarcoma shows no nuclear staining for INI1, (c) Epithelioid sarcoma shows positive staining for AE1/AE3, (d) Epithelioid sarcoma shows positive staining for EMA
-
29.58.
Markers for alveolar soft part sarcoma (Table 29.58)
Table 29.58 Markers for alveolar soft part sarcoma -
29.59.
Markers for Ewing sarcoma and primitive neuroectodermal tumor (ES/PNET) (Table 29.59)
Table 29.59 Markers for Ewing sarcoma and primitive neuroectodermal tumor (ES/PNET) Fig. 29.9 
(a) Ewing sarcoma shows positive staining for FLI1, (b) Ewing sarcoma/PNENT shows positive staining for NKX2.2
-
29.60.
Markers for synovial sarcoma (Table 29.60)
Table 29.60 Markers for synovial sarcoma Fig. 29.10 
(a) Synovial sarcoma on H&E section, (b) Synovial sarcoma shows positive staining for TLE1
-
29.61.
Markers for desmoplastic small round cell tumor (Table 29.61)
Table 29.61 Markers for desmoplastic small round cell tumor Fig. 29.11 
(a) DSRCT on H&E section, (b) DSRCT shows positive staining for WT1, (c) DSRCT shows positive staining for desmin, (d) DSRCT shows positive staining for AE1/AE3
-
29.62.
Markers for malignant extrarenal rhabdoid tumor (Table 29.62)
Table 29.62 Markers for malignant extrarenal rhabdoid tumor
Bone Tumors
-
29.63.
Markers for mesenchymal chondrosarcoma (Table 29.63)
Table 29.63 Markers for mesenchymal chondrosarcoma -
29.64.
Markers for chordoma (Table 29.64)
Table 29.64 Markers for chordoma -
29.65.
Markers for adamantinoma (Table 29.65)
Table 29.65 Markers for adamantinoma -
29.66.
Markers for Langerhans cell histiocytosis (Table 29.66)
Table 29.66 Markers for Langerhans cell histiocytosis
Differential Diagnosis
-
29.67.
Inflammatory myofibroblastic tumor (IMT)/inflammatory fibrosarcoma (IF) vs. dendritic cell neoplasms (DCN) (Table 29.67)
Table 29.67 Inflammatory myofibroblastic tumor (IMT)/inflammatory fibrosarcoma (IF) vs. dendritic reticulum cell tumor (DCT) -
29.68.
Inflammatory myofibroblastic tumor (IMT)/inflammatory fibrosarcoma (IF) vs. sarcomatoid urothelial carcinoma (SUC) (Table 29.68)
Table 29.68 Inflammatory myofibroblastic tumor (IMT)/inflammatory fibrosarcoma (IF) vs. sarcomatoid urothelial carcinoma (SUC) -
29.69.
Myxoinflammatory fibroblastic sarcoma (MFS) vs. Hodgkin’s lymphoma (HL) (Table 29.69)
Table 29.69 Myxoinflammatory fibroblastic sarcoma (MFS) vs. Hodgkin’s lymphoma (HL) -
29.70.
Fibrosarcoma (CF) vs. monomorphic synovial sarcoma (MSS) vs. malignant peripheral nerve sheath tumor (MPNST) vs. spindle cell carcinoma (SCC) vs. spindle cell melanoma (SCM) vs. dermatofibrosarcoma protuberans (DFSP) vs. spindle cell rhabdomyosarcoma (SCR) vs. leiomyosarcoma (LMS) vs. spindle cell angiosarcoma (SCA) (Table 29.70)
Table 29.70 Fibrosarcoma (CF) vs. monomorphic synovial sarcoma (MSS) vs. malignant peripheral nerve sheath tumor (MPNST) vs. spindle cell carcinoma (SCC) vs. spindle cell melanoma (SCM) vs. Dermatofibrosarcoma protuberans (DFSP) vs. spindle cell rhabdomyosarcoma (SCR) vs. leiomyosarcoma (LMS) vs. spindle cell angiosarcoma (SCA) -
29.71.
Low grade fibromyxoid sarcoma (LGFS) vs. neurofibroma/perineurioma vs. desmoid tumors (Table 29.71)
Table 29.71 Low grade fibromyxoid sarcoma (LGFS) vs. neurofibroma/perineurioma vs. desmoid tumors -
29.72.
Juvenile xanthogranuloma (JXG)/reticulohistiocytoma (RC) vs. Langerhans cell histiocytosis (LCH) (Table 29.72)
Table 29.72 Juvenile xanthogranuloma (JXG)/reticulohistiocytoma (RC) vs. Langerhans cell histiocytosis (LCH) -
29.73.
Dermatofibroma protuberans (DFSP) vs. dermatofibroma (DF) vs. fibrosarcoma arising in DFSP (Table 29.73)
Table 29.73 Dermatofibroma protuberans (DFSP) vs. dermatofibroma (DF) vs. fibrosarcoma arising in DFSP -
29.74.
Rhabdomyosarcoma (RMS) vs. Ewing sarcoma/PNET (ES/PNET) vs. neuroblastoma (NB) vs. desmoplastic small round cell tumor (DSRCT) vs. small cell synovial sarcoma (SCSS) vs. lymphoma (Table 29.74)
Table 29.74 Rhabdomyosarcoma (RMS) vs. Ewing sarcoma/PNET (ES/PNET) vs. neuroblastoma (NB) vs. desmoplastic small round cell tumor (DSRCT) vs. synovial sarcoma (SS) vs. lymphoma -
29.75.
Leiomyoma vs. GIST vs. schwannoma (Table 29.75)
Table 29.75 Leiomyoma vs. GIST vs. schwannoma -
29.76.
Glomus tumors (GT) vs. hemangiopericytoma (HPC)/solitary fibrous tumor (SFT) of soft tissue (Table 29.76)
Table 29.76 Glomus tumors (GT) vs. hemangiopericytoma (HPC)/solitary fibrous tumor (SFT) of soft tissue -
29.77.
Kaposiform hemangioendothelioma (KH) vs. capillary hemangioma (CH) (Table 29.77)
Table 29.77 Kaposiform hemangioendothelioma (KH) vs. juvenile capillary hemangioma (CH) -
29.78.
Neurofibroma vs. schwannoma vs. perineurioma (Table 29.78)
Table 29.78 Neurofibroma vs. schwannoma vs. perineurioma -
29.79.
ES/PNET vs. lymphoblastic lymphoma (Table 29.79)
Table 29.79 ES/PNET vs. lymphoblastic lymphoma (LL) -
29.80.
ES/PNET vs. neuroblastoma (Table 29.80)
Table 29.80 ES/PNET vs. neuroblastoma -
29.81.
Chordoma vs. chondrosarcoma (Table 29.81)
Table 29.81 Chordoma vs. chondrosarcoma -
29.82.
Chordoma vs. renal cell carcinoma (Table 29.82)
Table 29.82 Chordoma vs. renal cell carcinoma -
29.83.
Langerhans cell histiocytosis (LCH) vs. Hodgkin lymphoma (HL) (Table 29.83)
Table 29.83 Langerhans’ cell histiocytosis (LCH) vs. Hodgkin lymphoma (HL) -
29.84.
Epithelioid sarcoma (ES) vs. epithelioid angiosarcoma (EA) vs. epithelioid malignant peripheral nerve sheath tumor (EPNST) vs. epithelioid leiomyosarcoma (ELMS) vs. sclerosing epithelioid fibrosarcoma (SEF) vs. epithelioid osteosarcoma (EO) (Table 29.84)
Table 29.84 Epithelioid sarcoma (ES) vs. epithelioid angiosarcoma (EA) vs. epithelioid malignant peripheral nerve sheath tumor (EPNST) vs. epithelioid leiomyosarcoma (ELMS) vs. sclerosing epithelioid fibrosarcoma (SEF) vs. epithelioid osteosarcoma (EO) -
29.85.
Rhabdomyoma vs. granular cell tumor (Table 29.85)
Table 29.85 Rhabdomyoma vs. granular cell tumor -
29.86.
Rhabdomyosarcoma vs. leiomyosarcoma (Table 29.86)
Table 29.86 Rhabdomyosarcoma vs. leiomyosarcoma
Adipocytic Tumors
Fibroblastic and Fibrohistiocytic Tumors
Fibrohistiocytic tumors
Smooth Muscle Tumors
Tumors of Perivascular Cells
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Zhu, S., Miettinen, M.M., Lin, G. (2015). Soft Tissue and Bone Tumors. In: Lin, F., Prichard, J. (eds) Handbook of Practical Immunohistochemistry. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-1578-1_29
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DOI: https://doi.org/10.1007/978-1-4939-1578-1_29
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