Concise immunohistochemistry in carcinoma of unknown primary origin
Keywords:
Immunohistochemistry, carcinoma of unknown primary origin, cytokeratin, carcinomaAbstract
Carcinoma of unknown primary origin is a malignant epithelial neoplasm clinically defined by the presence of metastasis without known primary origin at the time of diagnosis. When it is clinically encountered, further investigations should be considered. Identification of primary origin of such neoplasm is crucial for proper patient management and prognosis. Immunohistochemistry has become an ancillary study for resolving this issue. Initial immunohistochemistry panel including AE1/AE3, S100, CD45 and vimentin is suggested for identification of lineage of tumor cell differentiation. If the tumor cells are diffusely positive for AE1/AE3 confirming the diagnosis of carcinoma, additional immunohistochemistry markers including CK7, CK20 and other tissue-specific markers should be employed in order to determine a primary origin. Interpretation of immunohistochemistry should always be correlated with histopathological findings, clinical context and radiological information. This approach can facilitate determination of the type and origin of carcinoma of unknown primary origin.
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Blaszyk H, Hartmann A, Bjornsson J. Cancer of unknown primary: clinicopathologic correlations. APMIS 2003;111:1089-94. https://doi.org/10.1111/j.1600-0463.2003.apm1111203.x
Yakushiji S, Ando M, Yonemori K, Kohno T, Shimizu C, Katsumata N, et al. Cancer of unknown primary site: review of consecutive cases at the National Cancer Center Hospital of Japan. Int J Clin Oncol 2006;11:421-5. https://doi.org/10.1007/s10147-006-0599-9
Chetty R. Cytokeratin expression in cauda equina paragangliomas. Author's response to letter. Am J Surg Pathol 1999;23:491. https://doi.org/10.1097/00000478-199904000-00021
Kumar V, Abbas AK, Aster JC. Neoplasia. In: Kumar V, Abbas AK, Aster JC. Robbins basic pathology. 10th ed. Philadelphia: Elsevier; 2018. p.189-242.
Hammar SP. Metastatic adenocarcinoma of unknown primary origin. Hum Pathol 1998;29: 1393-402.
https://doi.org/10.1016/S0046-8177(98)90007-7
Ross MH, Pawlina W. Cell cytoplasm. In: Ross MH, Pawlina W. Histology: a text and atlas with correlated cell and molecular biology. 7th ed. Philadelphia: Lippincott Williams & Wilkins;2016. p.23-73.
Spagnolo DV, Michie SA, Crabtree GS, Warnke RA, Rouse RV. Monoclonal anti-keratin (AE1) reactivity in routinely processed tissue from 166 human neoplasms. Am J Clin Pathol 1985; 84:697-704.
https://doi.org/10.1093/ajcp/84.6.697
Rekhtman N, Bishop JA. Quick reference handbook for surgical pathologists. Berlin, Heidelberg: Springer Berlin Heidelberg; 2011. https://doi.org/10.1007/978-3-642-20086-1
Lin F, Liu H. Immunohistochemistry in undifferentiated neoplasm/tumor of uncertain origin. Arch Pathol Lab Med 2014;138:1583-610. https://doi.org/10.5858/arpa.2014-0061-RA
Bhargava R, Dabbs DJ. Immunohistology of metastatic carcinoma of unknown primary site. In: Dabbs DJ, editor. Diagnostic immunohistochemistry: theranostic and genomic applications. 4th ed. Philadelphia: Elsevier/Saunders; 2014. p.204-44.
Mohamed A, Gonzalez RS, Lawson D, Wang J, Cohen C. SOX10 expression in malignant melanoma, carcinoma, and normal tissues. Appl Immunohistochem Mol Morphol 2013; 21:506-10.
https://doi.org/10.1097/PAI.0b013e318279bc0a
Willis BC, Johnson G, Wang J, Cohen C. SOX10: a useful marker for identifying metastatic melanoma in sentinel lymph nodes. Appl Immunohistochem Mol Morphol 2015;23: 109-12.
https://doi.org/10.1097/PAI.0000000000000097
O'Malley DP, Grimm KE, Banks PM. Immunohistology of non-Hodgkin lymphoma. In: Dabbs DJ, editor. Diagnostic immunohistochemistry: theranostic and genomic applications. 4th ed. Philadelphia: Elsevier/ Saunders; 2014. p.148-88.
Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, editors. WHO classification of tumours of haematopoietic and lymphoid tissues. Revised 4th ed. Lyon:IARC; 2017.
Chu PG, Weiss LM. Expression of cytokeratin 5/6 in epithelial neoplasms: an immunohistochemical study of 509 cases. Mod Pathol. Mod Pathol 2002;15:6-10. https://doi.org/10.1038/modpathol.3880483
Kaufmann O, Fietze E, Mengs J, Dietel M. Value of p63 and cytokeratin 5/6 as immunohistochemical markers for the differential diagnosis of poorly differentiated and undifferentiated carcinomas. Am J Clin Pathol 2001;116:823-30. https://doi.org/10.1309/21TW-2NDG-JRK4-PFJX
Travis WD, Brambilla E, Burke AP, Marx A, Nicholson AG, editors. WHO classification of tumours of the lung, pleura, thymus and heart. 4th ed. Lyon: IARC; 2015.
de Sanjose S, Quint WG, Alemany L, Geraets DT, Klaustermeier JE, Lloveras B, et al. Human papillomavirus genotype attribution in invasive cervical cancer: a retrospective cross-sectional worldwide study. Lancet Oncol 2010;11:1048-56. https://doi.org/10.1016/S1470-2045(10)70230-8
Kurman RJ, Carcangiu ML, Herrington CS, Young RH, editors. WHO classification of tumours of female reproductive organs. 4th ed. Lyon: IARC; 2014.
El-Naggar AK, Chan JKC, Grandis JR, Takata T, Slootweg PJ, editors. WHO classification of head and neck tumours. 4th ed. Lyon: IARC; 2017.
Chu P, Wu E, Weiss LM. Cytokeratin 7 and cytokeratin 20 expression in epithelial neoplasms: a survey of 435 cases. Mod Pathol 2000;13:962-72. https://doi.org/10.1038/modpathol.3880175
Krasinskas AM, Goldsmith JD. Immunohistology of the gastrointestinal tract. In: Dabbs DJ, editor. Diagnostic immunohistochemistry: theranostic and genomic applications. 4th ed. Philadelphia: Elsevier/Saunders; 2014. p.508-39.
Bayrak R, Yenid¬nya S, Haltas H. Cytokeratin 7 and cytokeratin 20 expression in colorectal adenocarcinomas. Pathol Res Pract 2011 15; 207:156-60. https://doi.org/10.1016/j.prp.2010.12.005
Bhargava R, Dabbs DJ. Immunohistology of the breast. In: Dabbs DJ, editor. Diagnostic immunohistochemistry: theranostic and genomic applications. 4th ed. Philadelphia: Elsevier/Saunders; 2014. p.738-9.
Cimino-Mathews A, Subhawong AP, Illei PB, Sharma R, Halushka MK, Vang R, et al. GATA3 expression in breast carcinoma: utility in triple-negative, sarcomatoid, and metastatic carcinomas. Hum Pathol 2013;44: 1341-9. https://doi.org/10.1016/j.humpath.2012.11.003
Schwartz LE, Begum S, Westra WH, Bishop JA. GATA3 immunohistochemical expression in salivary gland neoplasms. Head Neck Pathol 2013;7:311-5. https://doi.org/10.1007/s12105-013-0442-3
Liu H, Shi J, Wilkerson ML, Lin F. Immunohistochemical evaluation of GATA3 expression in tumors and normal tissues: a useful immunomarker for breast and urothelial carcinomas. Am J Clin Pathol 2012;138: 57-64. https://doi.org/10.1309/AJCP5UAFMSA9ZQBZ
Bosman FT, Carneiro F, Hruban RH, Theise ND, editors. WHO classification of tumours of the digestive system. 4th ed. Lyon: IARC; 2010.
Magnusson K, de Wit M, Brennan DJ, Johnson LB, McGee SF, Lundberg E, et al. SATB2 in combination with cytokeratin 20 identifies over 95% of all colorectal carcinomas. Am J Surg Pathol 2011;35:937-48.
https://doi.org/10.1097/PAS.0b013e31821c3dae
Dragomir A, de Wit M, Johansson C, Uhlen M, Pont é n F. The role of SATB2 as a diagnostic marker for tumors of colorectal origin: Results of a pathology-based clinical prospective study. Am J Clin Pathol 2014;141:630-8. https://doi.org/10.1309/AJCPWW2URZ9JKQJU
Conner JR, Hornick JL. SATB2 is a novel marker of osteoblastic differentiation in bone and soft tissue tumours. Histopathology 2013;63: 36-49. https://doi.org/10.1111/his.12138
Moch H, Humphrey PA, Ulbright TM, Reuter VE, editors. WHO classification of tumours of the urinary system and male genital organs. 4th ed. Lyon: IARC; 2016. https://doi.org/10.1016/j.eururo.2016.02.028
Gurel B, Ali TZ, Montgomery EA, Begum S, Hicks J, Goggins M, et al. NKX3.1 as a marker of prostatic origin in metastatic tumors. Am J Surg Pathol 2010;34:1097-105.
https://doi.org/10.1097/PAS.0b013e3181e6cbf3
Molini V, Balaton A, Rotman S, Mansouri D, De Pinieux I, Homsi T, et al. Alpha-methyl CoA racemase expression in renal cell carcinomas. Hum Pathol 2006;37:698-703.
https://doi.org/10.1016/j.humpath.2006.01.012
Evans AJ. -Methylacyl CoA racemase (P504S): overview and potential uses in diagnostic pathology as applied to prostate needle biopsies. J Clin Pathol 2003;56:892-7.
https://doi.org/10.1136/jcp.56.12.892
Higgins JP, Kaygusuz G, Wang L, Montgomery K, Mason V, Zhu SX, et al. Placental S100 (S100P) and GATA3: markers for transitional epithelium and urothelial carcinoma discovered by complementary DNA microarray. Am J Surg Pathol 2007;31: 673-80.
https://doi.org/10.1097/01.pas.0000213438.01278.5f
Timek DT, Shi J, Liu H, Lin F. Arginase-1, HepPar-1, and Glypican-3 are the most effective panel of markers in distinguishing hepatocellular carcinoma from metastatic tumor on fine-needle aspiration specimens. Am J Clin Pathol 2012;138:203-10. https://doi.org/10.1309/AJCPK1ZC9WNHCCMU
Radwan NA, Ahmed NS. The diagnostic value of arginase-1 immunostaining in differentiating hepatocellular carcinoma from metastatic carcinoma and cholangiocarcinoma as compared to HepPar-1. Diagn Pathol 2012;7: 149 https://doi.org/10.1186/1746-1596-7-149
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