Cytological Pattern Profiling of Tumors from Different Visceral Sites

  • Giorgio Gherardi


The cytological findings in FNB samples from the large majority of primary and secondary tumors detected in visceral sites, as well as those of metastatic tumors appearing in lymph nodes or soft tissues, can be classified according to the principles of pattern analysis. In the given case, this approach first requires identifying the specific category that the constituent cells belong to and then, if possible, classifying the set of observed morphological changes according to distinctive cytological patterns. The description of cytological features should be reproducibly standardized. At least nine major cytomorphological cell types can be identified. These are listed in Table 5.1. Each category includes a variable number of possible distinctive patterns. Once the major pattern has been identified, the diagnostic possibilities are dramatically reduced. The next step is to reach a conclusive diagnosis by prudent deductive reasoning based on additional ancillary data and/or clinical findings. Although a definitive diagnosis is not always possible, the identification of a specific pattern is nonetheless of importance for further clinical management of the case.
Table 5.1

Major categories of cell morphology in FNB smears (excluding lymphoid lesions)


Renal Oncoc Ytoma Chromatin Texture Cellular Dissociation Ymph Node Drenal Cortex 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Tot T (2002) Cytokeratins 20 and 7 as biomarkers: usefulness in discriminating primary from metastatic adenocarcinoma. Eur J Cancer 38:758–763.CrossRefPubMedGoogle Scholar
  2. 2.
    Tot T (1999) Adenocarcinomas metastatic to the liver: the value of cytokeratins 20 and 7 in the search for unknown primary tumors. 85:171–177.Google Scholar
  3. 3.
    Moll R, Löwe A, Laufer J, Franke WW (1992) Cytokeratin 20 in human carcinomas. A new histodiagnostic marker detected by monoclonal antibodies. Am J Pathol 140:427–447.PubMedGoogle Scholar
  4. 4.
    Loy TS, Calaluce RD (1994) Utility of cytokeratin immunostaining in separating pulmonary adenocarcinomas from colonic adenocarcinomas. Am J Clin Pathol 102:764–767.PubMedGoogle Scholar
  5. 5.
    Lagendijk JH, Mullink H, Van Diest PJ et al (1998) Tracing the origin of adenocarcinomas with unknown primary using immunohistochemistry: differential diagnosis between colonic and ovarian carcinomas as primary sites. Hum Pathol 29:491–497.CrossRefPubMedGoogle Scholar
  6. 6.
    Loy TS, Calaluce RD, Keeney GL (1996) Cytokeratin immunostaining in differentiating primary ovarian carcinoma from metastatic colonic adenocarcinoma. Mod Pathol 9:1040–1044.PubMedGoogle Scholar
  7. 7.
    Lagendijk JH, Mullink H, Van Diest PJ et al (1998) Tracing the origin of adenocarcinomas with unknown primary using immunohistochemistry: differential diagnosis between colonic and ovarian carcinomas as primary sites. Hum Pathol 29:491–497.CrossRefPubMedGoogle Scholar
  8. 8.
    Tan J, Sidhu G, Greco MA et al (1998) Villin, cytokeratin 7, and cytokeratin 20 expression in pulmonary adenocarcinoma with ultrastructural evidence of microvilli with rootlets. Hum Pathol 29:390–396.CrossRefPubMedGoogle Scholar
  9. 9.
    Chu P, Wu E, Weiss LM (2000) Cytokeratin 7 and cytokeratin 20 expression in epithelial neoplasms: a survey of 435 cases. Mod Pathol 13:962–972.CrossRefPubMedGoogle Scholar
  10. 10.
    Wauters CC, Smedts F, Gerrits LG et al (1995) Keratins 7 and 20 as diagnostic markers of carcinomas metastatic to the ovary. Hum Pathol 26:852–855.CrossRefPubMedGoogle Scholar
  11. 11.
    Chuang WY, Yeh CJ, Chu PH (2008) Expression of thyroid transcription factor-1 in brain metastases: A useful indicator of pulmonary origin. J Clin Neurosci 15:643–646.CrossRefPubMedGoogle Scholar
  12. 12.
    Strickland-Marmol LB, Khoor A, Livingston SK, Rojiani A (2007) Utility of tissue-specific transcription factors thyroid transcription factor 1 and Cdx2 in determining the primary site of metastatic adenocarcinomas to the brain. Arch Pathol Lab Med 131:1686–1690.PubMedGoogle Scholar
  13. 13.
    Tanaka S, Saito K, Ito T et al (2007) CDX2 as a useful marker of colorectal adenocarcinoma metastases to lung in pre-operative biopsy specimens. Oncol Rep 18:87–92.PubMedGoogle Scholar
  14. 14.
    Zhang MQ, Lin F, Hui P et al (2007) Expression of mucins, SIMA, villin, and CDX2 in small-intestinal adenocarcinoma. Am J Clin Pathol 128:808–816.CrossRefPubMedGoogle Scholar
  15. 15.
    Hong SM, Cho H, Moskaluk CA et al (2005) CDX2 and MUC2 protein expression in extrahepatic bile duct carcinoma. Am J Clin Pathol 124:361–370.CrossRefPubMedGoogle Scholar
  16. 16.
    Kubba LA, McCluggage WG, Liu J et al (2008) Thyroid transcription factor-1 expression in ovarian epithelial neoplasms. Mod Pathol 21:485–490.CrossRefPubMedGoogle Scholar
  17. 17.
    Siami K, McCluggage WG, Ordonez NG et al (2007) Thyroid transcription factor-1 expression in endometrial and endocervical adenocarcinomas. Am J Surg Pathol 31: 1759–1763.CrossRefPubMedGoogle Scholar
  18. 18.
    Compérat E, Zhang F, Perrotin C et al (2005) Variable sensitivity and specificity of TTF-1 antibodies in lung metastatic adenocarcinoma of colorectal origin. Mod Pathol 18:1371–1376.CrossRefPubMedGoogle Scholar
  19. 19.
    Lei JY, Bourne PA, diSant’Agnese PA, Huang J (2006) Cytoplasmic staining of TTF-1 in the differential diagnosis of hepatocellular carcinoma vs cholangiocarcinoma and metastatic carcinoma of the liver. Am J Clin Pathol 125:519–525.PubMedGoogle Scholar
  20. 20.
    McCluggage WG, Shah R, Connolly LE, McBride HA (2008) Intestinal-type cervical adenocarcinoma in situ and adenocarcinoma exhibit a partial enteric immunophenotype with consistent expression of CDX2. Int J Gynecol Pathol 27:92–100.CrossRefPubMedGoogle Scholar
  21. 21.
    Ortiz-Rey JA, Alvarez C, San Miguel P et al (2005) Expression of CDX2, cytokeratins 7 and 20 in sinonasal intestinaltype adenocarcinoma. Appl Immunohistochem Mol Morphol 13:142–146.CrossRefPubMedGoogle Scholar
  22. 22.
    Herawi M, De Marzo AM, Kristiansen G, Epstein JI (2006) Expression of CDX2 in benign tissue and adenocarcinoma of the prostate. Hum Pathol 38:72–78.CrossRefPubMedGoogle Scholar
  23. 23.
    Mazziotta RM, Borczuk AC, Powell CA, Mansukhani M (2005) CDX2 immunostaining as a gastrointestinal marker: expression in lung carcinomas is a potential pitfall. Appl Immunohistochem Mol Morphol 13:55–60.CrossRefPubMedGoogle Scholar
  24. 24.
    Park S-Y, Kim BH, Kim JH et al (2007) Panels of immunohistochemical markers help determine primary sites of metastatic adenocarcinoma. Arch Pathol Lab Med 131:1561–1567.PubMedGoogle Scholar
  25. 25.
    Kontogianni K, Nicholson AG, Butcher D, Sheppard MN (2005) CD56: a useful tool for the diagnosis of small cell lung carcinomas on biopsies with extensive crush artefact. J Clin Pathol 58:978–980.CrossRefPubMedGoogle Scholar
  26. 26.
    Kaufmann O, Fietze E, Mengs J, Dietel M (2001) Value of p63 and cytokeratin 5/6 as immunohistochemical markers for the differential diagnosis of poorly differentiated and undifferentiated carcinomas. Am J Clin Pathol 116:823–830.CrossRefPubMedGoogle Scholar
  27. 27.
    Tsang WY, Chan JK, Lee KC et al (1991) Basaloid-squamous carcinoma of the upper aerodigestive tract and socalled adenoid cystic carcinoma of the oesophagus: the same tumour type? Histopathology 19:35–46.CrossRefPubMedGoogle Scholar
  28. 28.
    Banks ER, Frierson HF Jr, Mills SE et al (1992) Basaloid squamous cell carcinoma of the head and neck. A clinicopathologic and immunohistochemical study of 40 cases. Am J Surg Pathol 16:939–946.CrossRefPubMedGoogle Scholar
  29. 29.
    Wan SK, Chan JK, Tse KC (1992) Basaloid-squamous carcinoma of the nasal cavity. J Laryngol Otol 106:370–371.CrossRefPubMedGoogle Scholar
  30. 30.
    Nagel H, Hotze HJ, Laskawi R et al (1999) Cytologic diagnosis of adenoid cystic carcinoma of salivary glands. Diagn Cytopathol 20:358–366.CrossRefPubMedGoogle Scholar
  31. 31.
    Gupta RK, Green C, Naran S et al (1999) Fine-needle aspiration cytology of adenoid cystic carcinoma of the breast. Diagn Cytopathol 20:82–84.CrossRefPubMedGoogle Scholar
  32. 32.
    Hida CA, Gupta PK (1999) Cercariform cells: are they specific for transitional cell carcinoma? Cancer 87:69–74.CrossRefPubMedGoogle Scholar
  33. 33.
    Southgate J, Harnden P, Trejdosiewicz LK (1999) Cytokeratin expression patterns in normal and malignant urothelium: a review of the biological and diagnostic implications. Histol Histopathol 14:657–664.PubMedGoogle Scholar
  34. 34.
    Murali R, Delprado W (2005) CD10 immunohistochemical staining in urothelial neoplasms. Am J Clin Pathol 124:371–379.CrossRefPubMedGoogle Scholar
  35. 35.
    Azzopardi JG (1959) Oat-cell carcinoma of the bronchus. J Pathol Bacteriol 78:513–519.CrossRefPubMedGoogle Scholar
  36. 36.
    Jaffee IM, Rahmani M, Singhal MG, Younes M (2006) Expression of the intestinal transcription factor CDX2 in carcinoid tumors is a marker of midgut origin. Arch Pathol Lab Med 130:1522–1526.PubMedGoogle Scholar
  37. 37.
    Lin X, Saad RS, Luckasevic TM et al (2007) Diagnostic value of CDX-2 and TTF-1 expressions in separating metastatic neuroendocrine neoplasms of unknown origin. Appl Immunohistochem Mol Morphol 15:407–414.CrossRefPubMedGoogle Scholar
  38. 38.
    Alijo Serrano F, Sánchez-Mora N, Angel Arranz J et al (2007) Large cell and small cell neuroendocrine bladder carcinoma: immunohistochemical and outcome study in a single institution. Am J Clin Pathol 128:733–739.CrossRefPubMedGoogle Scholar
  39. 39.
    Carlson JW, Nucci MR, Brodsky J (2007) Biomarkerassisted diagnosis of ovarian, cervical and pulmonary small cell carcinomas: the role of TTF-1, WT-1 and HPV analysis. Histopathology 51:305–312.CrossRefPubMedGoogle Scholar
  40. 40.
    Pulitzer MP, Amin BD, Busam KJ (2009) Merkel cell carcinoma: review. Adv Anat Pathol 16:135–144.CrossRefPubMedGoogle Scholar
  41. 41.
    Folpe AL, Goldblum JR, Rubin BP et al (2005) Morphologic and immunophenotypic diversity in Ewing family tumors: a study of 66 genetically confirmed cases. Am J Surg Pathol 29:1025–1033.PubMedGoogle Scholar
  42. 42.
    Delattre O, Zucman J, Melot T et al (1994) The Ewing family of tumors—a subgroup of small-round-cell tumors defined by specific chimeric transcripts. N Engl J Med 331:294–299.CrossRefPubMedGoogle Scholar
  43. 43.
    Parham DM, Webber B, Holt H et al (1991) Immunohistochemical study of childhood rhabdomyosarcomas and related neoplasms. Results of an Intergroup Rhabdomyosarcoma study project. Cancer 67:3072–3080.CrossRefPubMedGoogle Scholar
  44. 44.
    Mooi WJ, Deenik W, Peterse JL, Hogendoorn PCW (1995) Keratin immunoreactivity in melanoma of soft parts (clear cell sarcoma). Histopathology 27:61–65CrossRefPubMedGoogle Scholar
  45. 45.
    Selby WL, Nance KV, Park HK (1992) CEA immunoreactivity in metastatic malignant melanoma. Mod Pathol 5:415–419.PubMedGoogle Scholar
  46. 46.
    Miller RT (2005) Immunohistochemistry in the differential diagnosis of clear cell carcinoma from the kidney, liver, and lung. Propath Immunohistochemistry Newsletter Scholar
  47. 47.
    Kumar D and Kumar S (1993) Adrenal cortical adenoma and adrenal metastasis of renal cell carcinoma: immunohistochemical and DNA ploidy analysis. Mod Pathol 6:36–40.PubMedGoogle Scholar
  48. 48.
    Nappi O, Ferrara G, Wick MR (1999) Neoplasms composed of eosinophilic polygonal cells: an overview with consideration of different cytomorphologic patterns. Semin Diagn Pathol 16:82–90.PubMedGoogle Scholar
  49. 49.
    Kumashiro Y, Yao T, Aishima S et al (2007) Hepatoid adenocarcinoma of the stomach: histogenesis and progression in association with intestinal phenotype. Hum Pathol 38:857–863.CrossRefPubMedGoogle Scholar
  50. 50.
    Ozolek JA, Bastacky SI, Myers EN, Hunt JL (2005) Immunophenotypic comparison of salivary gland oncocytoma and metastatic renal cell carcinoma. Laryngoscope 115:1097–1100.CrossRefPubMedGoogle Scholar
  51. 51.
    Zubovits J, Buzney E, Yu L, Duncan LM (2004) HMB-45, S-100, NK1/C3, and MART-1 in metastatic melanoma. Hum Pathol 35:217–223.CrossRefPubMedGoogle Scholar
  52. 52.
    Pelmus M, Guillou L, Hostein I (2002) Monophasic fibrous and poorly differentiated synovial sarcoma: immunohistochemical reassessment of 60 t(X;18)(SYT-SSX)-positive cases. Am J Surg Pathol 26:1434–1440.CrossRefPubMedGoogle Scholar
  53. 53.
    Lewis JS, Ritter JH, El-Mofty S (2005) Alternative epithelial markers in sarcomatoid carcinomas of the head and neck, lung, and bladder-p63, MOC-31, and TTF-1. Mod Pathol 18:1471–1481.CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Italia 2009

Authors and Affiliations

  • Giorgio Gherardi
    • 1
    • 2
  1. 1.Institute of Anatomic Pathology and CytopathologyFatebenefratelli HospitalMilanItaly
  2. 2.Postgraduate School of Anatomic PathologyUniversity of MilanItaly

Personalised recommendations