Russell K. Brynes, Nancy Klipfel, and Dennis A. Casciato
Appendix C1 Microscopic Clues of Tumor Origin
Appendix C2 Selected Immunohistochemical Tumor Markers
Appendix C3 Immunohistochemistry Diagnostic Algorithms
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I. |
Immunohistochemistry Diagnostic Algorithm Based On General Histology |
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II. |
Immunohistochemistry Diagnostic Algorithm for Carcinoma of Unknown Origin |
Appendix C4 Expected Immunophenotypes of Tumors
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I. |
Expected Immunophenotypes for Specific Malignant Cell Types |
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II. |
Small Blue Cell Tumors |
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III. |
Mesenchymal Tumors |
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IV. |
Liver, Pancreas, and Biliary Tract |
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V. |
Neural Tumors |
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VI. |
Germ-Cell and Sex Cord Stromal Tumors |
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VII. |
Skin Tumors |
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VIII. |
Tumors of Unknown Origin |
Appendix C5 Discriminatory Immunophenotypes for Lymphocytic Neoplasms
Appendix C6 World Health Organization Classification of Neoplastic Diseases of Lymphoid Tissues, 2008
Appendix C7 Acute Leukemias: Cytology, Immunophenotype, and the 2008
World Health Organization (WHO) Classification
Appendix C1 Microscopic Clues of Tumor Origin
PAS, periodic acid-Schiff; PNET, primitive neuroectodermal tumor.
Appendix C2 Selected Immunohistochemical Tumor Markers
DFSP, dermatofibrosarcoma protuberans; GIST, gastrointestinal stromal tumor; NET, neuroendocrine tumors (small cell carcinoma, Merkel cell carcinoma, and carcinoid tumors; paragangliomas; pheochromocytoma; neuroblastic tumors); PEComas, perivascular epithelioid cell tumors; PNET, primitive neuroectodermal tumor; SFT/HPC, solitary fibrous tumor/hemangiopericytoma
Appendix C3 Immunohistochemistry Diagnostic Algorithms
I. Immunohistochemistry Diagnostic Algorithm based on General Histology
II. Immunohistochemistry Diagnostic Algorithm for Carcinoma of Unknown Origin
+, positive; 0 or –, negative; CD, clusters of differentiation; CK, cytokeratin; ER, estrogen receptor; HepPar-1, hepatocyte paraffin-1; GCDFP-15, gross cystic disease fluid protein-15; PR, progesterone receptor; PSA, prostate-specific antigen; RCC, renal cell carcinoma; TTF, thyroid transcription factor See Appendix C4.IX for expanded evaluations of carcinoma of unknown origin.
aGlandular, squamoid, epithelioid, small cell, large cell, spindle cell
Modified from Voigt JJ, Mathieu MC, Bibeau F. The advent of immunohistochemistry in carcinoma of unknown primary site: a major progress. In: Fizazi K, ed. Carcinoma of an Unknown Primary Site. New York: Taylor & Francis; 2006:25–35.
Appendix C4 Expected Immunophenotypes of Tumors
I. Expected Immunophenotypes for Specific Malignant Cell Types
II. Small Blue Cell Tumors
A. Small blue cell tumors in adults
aPunctate pattern
B. Small blue cell tumors in children
aMuscle markers: Desmin, MSA, MyoD1, myogenin.
III. Mesenchymal Tumors
aPleomorphic high-grade sarcoma was previously designated malignant fibrous histiocytoma.
IV. Liver, Pancreas, and Biliary Tract
aCanalicular pattern; same pattern seen with polyclonal CEA.
V. Neural Tumors
aSustentacular cells surrounding the zellballen are S100+.
VI. Germ-Cell and Sex Cord Stromal Tumors
aPositive in syncytiocytotrophoblasts.
bnegative for EMA.
VII. Skin Tumors
aHigh-molecular-weight keratin.
VIII. Tumors of Unknown Origin
Key to all parts of Appendix C4: +, Positive; − or 0, negative; AFP, α-fetoprotein; AMACR, P504S α-methylacyl-CoA racemase; CA, cancer antigen; Calc, calcitonin; CD, clusters of differentiation; CD45, leukocyte common antigen (LCA); CEA, carcinoembryonic antigen; CK,cytokeratins; Des, desmin; EMA, epithelial membrane antigen; GCDFP-15, gross cystic disease fluid protein-15; GFAP, glial fibrillary acid protein; GYN, gynecologic cancers; hCG, human chorionic gonadotropin; HepPar-1, hepatocyte paraffin-1; Inh, inhibin; LCA, leukocyte common antigen (CD45); mCEA, monoclonal CEA; MEL, melanocyte markers, HMB-45 and Mart-1 (Melan-A); Musc, muscle markers (Des, MSA, MyoD1); MyoD1, striated muscle specific; MSA, muscle-specific actin; NET, neuroendocrine tumor markers: neuron-specific enolase (NSE), chromogranin, and synaptophysin (Syn), CD56, and CD57; Oct4, octamer transcription factor 4; PAP, prostatic acid phosphatase; PLAP, placental alkaline phosphatase; PNET, primitive neuroectodermal tumor; PSA, prostate-specific antigen; RCC, renal cell carcinoma; S100,S100 protein; SMA, smooth muscle actin; Thyg, thyroglobulin; TTF-1, thyroid transcription factor-1; TFE3, transcription factor-E3; TLE1, transducin-like enhancer of split 1; Vim, vimentin; vWF, von Willebrand factor (factor VIII–related antigen)
Appendix C5 Discriminatory Immunophenotypes for Lymphocytic Neoplasms
[X], occasionally positive
ALK-1, anaplastic lymphoma kinase [upregulated by t(2;5) in ALCL]; BCL, breakpoint cluster location (BCL-2 is positive in MCL, most FL, CLL/SLL, and some DLBCL; BCL-6 is positive in FL and some DLBCL); BOB.1 positive in Reed-Sternberg cells of lymphocyte-predominant Hodgkin lymphoma; CD, clusters of differentiation; CD45, leukocyte common antigen (LCA); CNS, central nervous system; Cyclin D1 (BCL-1) is positive in MCL, some HCL, and plasma cell malignancies; CXCL13, C-X-C motif chemokine 13; EBER, EBV-encoded RNA; EBV, Epstein-Barr virus; EMA, epithelial membrane antigen; FMC7, B-cell surface antigen found on mantle cell lymphoma, follicular lymphoma, and HCL; HHV8, human herpes virus type 8; HLA-DR, human leukocyte antigen-DR; HTLV-1, human T-cell lymphotropic virus type I; Igs, immunoglobulins; L & H, lymphocytic and histiocytic; MGUS, monoclonal gammopathy of undermined significance; MUM-1, multiple myeloma oncogene-1; NK, natural killer; OCT2 positive in Reed-Sternberg cells of lymphocyte-predominant Hodgkin lymphoma; Pax-5, pan-B antigen positive in B-cell lymphomas and in lymphocyte-predominant and classical Hodgkin lymphomas; PD-1, programmed death-1; TCL1, T-cell leukemia lymphoma protein 1; TCR, T-cell receptor protein (TCRαβ recognizes αβ chains of the TCR; TCRγδ recognizes the γδ chains of the TCR); Tdt, terminal deoxytransferase (positive in cortical thymic lymphoid cells and lymphoblastic neoplasms); TIA-1, T-cell intracellular antigen (found in cytotoxic T-cell and NK-cell cytoplasmic granules); TRAP, tartrate-resistant acid phosphatase
Appendix C6 World Health Organization Classification of Neoplastic Diseases of Lymphoid Tissues, 2008a
ALK-1, anaplastic lymphoma kinase; ALL, acute lymphoblastic leukemia; AIDS, acquired immunodeficiency syndrome; CLL / SLL, chronic lymphocytic leukemia / small lymphocytic lymphoma; HTLV-1, human T-cell lymphotropic virus type I; L & H, lymphocytic and histiocytic; NHL, non-Hodgkin lymphoma; NK, natural killer; NOS, not otherwise specified; PCL, primary cutaneous lymphomas; POEMS, polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes
aLymphoma grades: L, low; M, intermediate/high; H, high; V, variable
Extracted from Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW. World Health Organization classification of tumours of haematopoietic and lymphoid tissues. Lyon, France: IARC Press; 2008.
Appendix C7 Acute Leukemias
Acute Leukemias: Cytology, Immunophenotype, and the 2008 World Health Organization (WHO) Classification
Adapted from Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW. World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues. Lyon, France: IARC Press; 2008.
Legend to Appendix C7
++, strongly positive; +, usually positive or present; ±, variable; —, usually negative, absent, or weak; N, nuclei; G, cytoplasmic granules; AR, Auer rods
ALL, acute lymphoblastic leukemia; DIC, disseminated intravascular coagulation; Gp, platelet glycoprotein; LYS, lysozyme (muramidase); MPO, myeloperoxidase and Sudan black B; M0 - M7, categories of AML defined by the older French-American-British system; MS, myeloid sarcoma; NPM, nucleophosmin; NOS, not otherwise specified; NSE, nonspecific esterase; PPH, pseudo-Pelger-Huet anomaly; TdT, terminal deoxytransferase
Note:
Panmyeloid antigens: CD13, CD33, and CD117
Hematopoietic progenitor cell antigens: CD34, HLA-DR
Monocytic antigens: CD11b, CD14 (also CD4, CD11c, CD56, CD64)
Increased lysozyme levels are measured in the serum and characterize mixed (AMML) or pure (AMoL) monocytic leukemias.