Tag Archives: CD99

Organ Systems

Small Round Blue Cell Tumor

The small round blue cell tumor differential includes a wide variety of neoplasms, which in their purest form are morphologically indistinguishable from each other, and are dependent upon IHC and/or molecular studies for classification.  The differential diagnosis includes:  carcinoma, melanoma, lymphoma, rhabdomyosarcoma, PNET, and desmoplastic small round blue cell tumor.
 
An easy way to remember the IHC panel is to look at one’s hand.  Each finger is a stain, and the thumb is always CD99.  The 5 stain panel includes:  AE1/AE3, S-100, CD45, Desmin, and CD99.
 
Stain
Comments
AE1/AE3 positivity only is c/w a carcinoma, and f/u with a CK7/CK20 profile panel and neuroendocrine markers (chromo. A, synaptophysin, CD56) is recommended.  Co-expression of AE1/AE3 and desmin in the SRBCT setting is c/w a desmoplastic small round blue cell tumor.  Co-expression of CD99 and AE1/AE3 may also suggest a poorly differentiated synovial sarcoma.
S-100 positivity is suggestive of a melanoma.  Follow-up with melanoma specific markers is recommended (HMB-45, MART-1, etc.).
CD45 expression is c/s a lymphoma, and appropriate  follow-up markers (CD3, CD20, etc.) is recommended.
Desmin positivity in isolation in the SRBCT setting is c/w a rhabdomyosarcoma (Myogenin or Myo-D1+ and WT1=) or Wilms Tumor (Myogenin and Myo-D1= and WT1+).
CD99 expression only is c/w a EWS/PNET.  It should be noted that almost any other SRBCT may also express CD99 in some cases, and interpretation of CD99 in isolation, without AE1/AE3, Desmin, CD45, and S-100 is NOT recommended.
 
This 5 stain panel is only a screening panel, and more specific stains need to be followed up (e.g. HMB-45 = melanoma, myogenin = rhabdomyosarcoma, CK7/CK20 to further classify carcinomas).  An important note, CD99 is the “thumb” because the stain should only be used with the other 4 stains in the panel.  While CD99 is fairly sensitive for PNETs, it is NOT specific, and almost everything else on the differential list has been shown to occasionally stain with CD99.  If all five markers on the screening panel are negative, then one may consider several possibilities:  neuroblastoma (neuroendocrine marker +), lymphoproliferative d/o not expressing CD45 (leukemia, etc. – add CD43), or a carcinoma without AE1AE3 expression (use a second pan keratin marker with a differing cocktail, e.g. CAM5.2).
References
Arch Pathol Lab Med. Vol 132, March 2008.
 
Kandukuri SR, Lin F, Gui L, Gong Y, Fan F, Chen L, et al. Application of Immunohistochemistry in Undifferentiated Neoplasms: A Practical Approach. Arch Pathol Lab Med. 2017;141: 1014–1032. doi:10.5858/arpa.2016-0518-RA
CD Markers, Antibody List

CD99

CD99 (MIC-2 or p30/32) has an unknown function, but has been found to be expressed in vitally all cases of primitive neuroectodermal tumors (PNETs) and Ewing sarcoma.  The specificity is more limited and may be seen in alveolar rhabdomyosarcomas (15%), ALLs (90%), neuroendocrine carcinomas (20%), melanomas, etc.  Therefore, CD99 should not be interpreted alone, and is best used as part of a panel (e.g. AE1/AE3, desmin, S-100, and CD45 in an undifferentiated small round blue cell tumor situation).
 
Note:  CD99 was originally described as being sensitive and “specific” for PNETs.  However, expression in a variety of other tumors (including tumors with similar morphologies to PNETs) were also found to have expression (at least in a subset of cases).  Sensitivity of “new” IHC markers can be determined with a fair degree of accuracy using tissue arrays and large tumor libraries, but it usually takes time with efforts from many different laboratories to fully characterize the “specificity” of a marker.  This should always be taken into consideration when relying heavily on a “new” marker for diagnostic significance.
CD99 Expression Pattern
  • PNETs
  • Ewing Sarcoma
  • ALL (90%)
  • AML (subset)
  • ALCL (50-70%)
  • Solitary Fibrous Tumors
  • Numerous other neoplasms (not specific)
  • SHOULD NOT BE INTERPRETED IN ISOLATION!!
References
Wick, MR. “Immunohistochemical approaches to the diagnosis of undifferentiated malignant tumor.”Annals of Diagnostic Pathology12(2008):72-84.
 
Bone Marrow IHC.  Torlakovic, EE, et. al. American Society for Clinical Pathology Pathology Press © 2009.  pp. 123-124.
 
Rao, N., Colby, T. V., Falconieri, G., Cohen, H., Moran, C. A., & Suster, S. (2013). Intrapulmonary solitary fibrous tumors: clinicopathologic and immunohistochemical study of 24 cases. The American Journal of Surgical Pathology, 37(2), 155–166. doi:10.1097/PAS.0b013e31826a92f5