33 yrs old female underwent excisional biopsy from large nonresectable mediastinal mass with slight compression symtoms (cough). At the time of diagnosis multiple bilateral pulmonary mts were detected. 2 nodes removed with reactive changes. Platinum based chemo is planned. The surgeons mentioned an impression of very fast growth of the tumor.  
HISTO: Undifferentiated large cell nests with "discordant" and prominent ekstracellular keratinisation.  
IH: p63(+++)100%; CD5(-); CK5(+/++) 30% ; PanCK(++) 100% CD30(-); P16(-); CD34(-); PLAP(-); CD117(+/-)(faint) 20%; CEA(-); Ki67 ~60%.  
 
PROPOSAL: Poorly differentiated (highly keratinised) carcinoma: most probably primary mediastinal carcinoma, asociated with t(15;19) translocation (NUT midline carcinoma).  
DIFFERENTIAL (FISH or IH for NUT is required...): PROBABILITIES, AGE AJUSTED:  
1. Pulmonary (young age; Xray multiple bilobary mts);  
2. Thymic (CK5(-); young age; CD117+ (faint)  
3. Head/neck and cervical (p16(-); clinically CT pending; no symptoms).  
4. Somatic carcinoma from GCT (serum markers are negative; rarity for woman).  
 
Thank you for discussion.

kunze 2011-02-24 11:45	I support your concept of a NUT-carcinoma, provided the corresponding translocation will be confirmed. But so far, a thymic origin cannot be ruled out. About 50% of thymic SCCs are CD5-negative. The weak expression of CD117 is an argument against a primary pulmonary SCC.
ugnius 2011-02-24 11:52	Thank you. I will try to get NUT IH confirmation outside and inform all who may concern.
dalquen 2011-02-26 23:51	I agree with Prof. Kunze: NUT or thymic origin. The isles of keratinized cells seem to simulate thymus tissue.
dalquen 2011-02-27 10:41	I want to specify my comment: The islets of squamoid cells seem to imitate Hassall corpuscles of the thymic medulla. So I think that the tumour developed from a thymic precursor cell. Do the squamoid cells contain glycoprotein (PAS+)? This is a typical finding of Hassall cells. I think, the tumour cells should be negative for TTF1.
tzankov 2011-06-01 07:34	Dear Dr. Mickys, dear Ugnius,     Thank you very much for sending me this interesting case of a squamous carcinoma with a remarkable pilomatrical keratinisation. As discussed in the web I performed an additional staining for NUT1 in order to exclude a so called carcinoma with t(15;19). This tumor remained negative, so that this diagnosis cannot be established. Considering the morphology, the immune phenotype and the location of the primary tumor mass a thymic origin can be suspected but not proven, particularly in the face of the negativity for CD5. If you wish to offer to the clinicians a therapeutic target, we can perform sequency of the CD117 gene. Should we do that?
	» Add comment (Login)