title: Expression of cytokeratins and additional markers in undifferentiated lymph node metastases of the neck.
abstract: OBJECTIVE
  A variety of carcinomas (CA) can metastasize to the lymph nodes of the neck. Differentiation of CA in the lymph nodes according to their resemblance to the structure of origin is the basis of histopathological diagnosis. However, during the course of the disease, e.g. tumor recurrence after ablative surgery, these tissues can completely lose the ability to imitate typical structures of the organ that gave rise to malignant transformation. This can result in the inability of the pathologist to identify the origin of the metastases. The identification of the large group of cytokeratins (CK) as a member of the family of intermediate filaments has improved the diagnosis of epithelial tissues. An attempt was made to use CK antibodies to identify the organ of origin of poorly differentiated and anaplastic lymph node metastases of the neck.
  
  
  METHODS
  We investigated 34 routinely fixed (formalin/paraffin) lymph node metastases of the neck or specimens of these metastases. The tumors differed in terms of suspected primary tumor site and differentiation. Depending on the case history, diagnosis was performed by hematoxylin-eosin staining and by immunohistochemical staining of sections using antibodies against CK (CK nos. 1-10-11, 5-6, 6-8, 7, 8, 8-18, 13-15-16, 19 and 20) and against additional markers [vimentin, leukocyte common antigen (LCA), S-100, gross cystic disease fluid protein (GCDFP) and Epstein-Barr virus-induced latent membrane antigen (EBV-LMP)].
  
  
  RESULTS
  The histopathological diagnosis was lympho-epithelial CA (8 cases), thyroid gland CA (2 cases), mammary gland CA (5 cases), bronchial CA (4 cases), basaloid CA (3 cases), clear cell CA (2 cases), sebaceous CA (1 case) and pharyngeal CA (9 cases). Some metastases were anaplastic in differentiation (G3-4). The marker expression in the immunohistological sections supported the histopathological findings. In some cases diagnosis succeeded especially in evaluating the marker expression. For example, in lympho-epithelial CA the epithelial tumor cell formations were positive for CK 5-6 antibodies, while expression in the lymphatic cells was lacking. In mammary gland CA the tumor cells were clearly identified by their positivity for CK 7 and GCDFP antibodies, in contrast to the negative infiltrating cells surrounding the tumor cells.
  
  
  CONCLUSIONS
  In light of the case history details and the histopathological findings, immunohistological expression of various markers, especially the identification of CK subtypes, supported the differential diagnosis. In some cases the diagnosis may be established only by using CK profile and additional markers.
authors.affiliation: Department of Otorhinolaryngology, University Hospital, Martin Luther University Halle-wittenberg, Magdeburger Str. 12, 06097 Halle a. d. S., Germany.
authors.forename: S
authors.initials: S
authors.lastname: Bartel-Friedrich
authors.forename: R E
authors.initials: RE
authors.lastname: Friedrich
authors.forename: H J
authors.initials: HJ
authors.lastname: Holzhausen
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis*; D002454:Cell Differentiation; D006801:Humans; D007150:Immunohistochemistry; D007633:Keratins / Q000032:analysis*; D008207:Lymphatic Metastasis / Q000175:diagnosis* / Q000473:pathology; D009333:Neck; D009369:Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D009928:Organ Specificity; D011379:Prognosis
chemical_list: D014408:Biomarkers, Tumor; D007633:Keratins