LT TELEPATOLOGIJA

67 yrs female with clinically indolent disease, fatigue, lymphadenopathy.  
Axillary lymph node biopsy and threpine biopsy was performed. Unfortunatelly the patient was deceased soon after biopsy.  
FULL HISTORY: 2007 acute pneumonia and uncertain hepatosplenomegaly. 2008 deep anemia and transfusions. Massive visceral lymphadenopathy and hepatosplenomegaly, subfebrile fever. Due to positive blood culture (Gram(-)) the patient was hospitalized (sepsis). Infiltration in the left lung, pleuritis hypoechoic nodules up to 3cm in the spleen were found. Therapy: antibiotics, duretics and transfusions. Due to dyspnea and progressing bacteriemic shock the patient was deceased. The autopsy was declined. EBV evaluation was not done.  
HISTO: 1. NODE: Focal cHL picture with a reach of tumor cells areas DLBCL like.  
IH: CD20+; CD30+; CD15-; EBV LMP1+; LCA+; CylinD1-; EMA-; p53+; Mum1+; Bcl6- (single +, low quality); CD10-. BM: 2 deformed nidus of fibrosis with atypical cells (HL like picture):CD20+; CD30+/-; CD15- (LOW QUALITY).  
 
DIFFERENTIAL: CLASSIC EBV+ HOGDKIN'S LYMPHOMA (VARIANT?) vs EBV DRIVEN B LYMPHOPROLIFERATION/DLBCL.

yethuwin 2008-06-22 07:32	you should consider of lymphocyte-rich type hodgkin lymphoma.
tzankov 2008-06-23 09:52	Small cells are infected by EBV, the large cells are CD15-, CD45+, thus Hodgkin lymphoma apperas not to be the differential diagnosis of first choise. In a post-trabsplant setting I would call this disease Hodgkin-like PTLD, but here, without obvious imunocompromize, the most proper designation would be probably senile EBV+ LPD. Importnatly, these diseases are not "indolent".     see also:     Cancer Sci. 2008 Jun;99(6):1085-91. Age-related Epstein-Barr virus-associated B-cell lymphoproliferative disorders: special references to lymphomas surrounding this newly recognized clinicopathologic disease. Shimoyama Y, Yamamoto K, Asano N, Oyama T, Kinoshita T, Nakamura S.
ugnius 2008-06-23 11:37	Thank you. Please find full history of the patient. After clinicians: alcohol use anamnesis. EBV status is unclear.
tzankov 2008-06-23 13:43	Well, in my opinion (Tzankov A, Brunhuber T, Gschwendtner A, Brunner A. Incidental oral plasmablastic lymphoma with aberrant expression of CD4 in an elderly HIV-negative patient: how a gingival polyp can cause confusion. Histopathology. 2005; 46(3):348-50) alcoholism is an imunocompromizin factor; in addition the patient is >65. Thus, "senile EBV+ LPD" is still the best designation of the process.
hurwitz 2008-06-23 17:15	I have observed a number of practically identical cases, most of them incidental findings in elderly patients (>65), occuring often terminally (weeks before the pateint's death). Morphology identical to your case, HD-like cells, CD20+, CD45+, CD30+, and LMP1+.   I agree with Dr.Tzankov, this is an EBV driven lymphoprolifera- tion in an elderly patient. Factors in favour of immodefficiency are: age and alcoholism. Gram- septicemia is probably another expression of a deficient immune system.   I doubt that this is an indolent disease Is there any possibility to find out for how long the lymphadenopathy did exist ?
ugnius 2008-06-23 17:31	Thanx. The duration of lymphadenopathy at least 1 year.
k.naresh 2008-06-23 21:46	I am not sure if most of the large lymphoid cells are positive for CD45 (LCA). Much of the positivity is from the surrounding cells. CD45 is possibly negative in a good proportion of the large cells.     CD20 expression is also heterogeneous and some cells are negative.     I would interpret this case as classical Hodgkin lymphoma, which also involves the marrow (stage 4).
tzankov 2008-06-25 16:32	one very strong argument against hodgkin (along with the lacking pathognominic cells) is the distribution of the LMP1-positivity. if one assumes that this is a hodgkin, so a coincidental acute mononucleosis should be present as well, but this model would be, in face of the lacking expression of CD15 and the unequivocal expression of CD45 even in a proportion of tumor cells, rather hypothetic. as I mentioned previously, in a post-transplant setting this would be a hodgkin-like PTLD (an aggressive disease), but here the designation senile EBV+ LPD would be the most proper one. CD79a (in addition oct2 and bob.1) might be helpful (probably negative in HL and probably positive in LPD).
SergeyN 2008-06-25 21:53	"the key to distinguishing between these EBV+ B cell LPDs and EBV+ HL now depends on recognition of the degree of expression of B cell markers, such as CD20 and CD79a, on the tumor cells. EBV+ B cell LPD is always characterized by the expression of CD20 and CD79a and is associated with light chain restriction in many of large cells" (see http://www.jsltr.org/journal/46-1/4601_01.pdf)     I would support Dr.Tzankov's request for CD79a in differentiating cHL. Light chains could help, too.
torlakovic 2008-06-28 01:21	I would suggest to consider the difference in EBV latency status in this case. If LMP1+ and EBNA2 are positive, that would be latency type 3 and immunodeficiency-related, and if LMP1+ and EBNA2-, it would be latency type 2, which is compatible with cHL or some DLBCL. However, both PTLD and senile EBV-associated disease can also be type 2 in some cases. If EBNA2-, Oct2, BOB2, and PU.1 may help distinction between cHL and DLBCL. However, some cases remain classified as gray zone. In HIV+ patients, lymphocyte depleted cHL may be EBV+ and may have aggressive course. While the extent of B-cell markers and/or CD45 may be helpful, many variations have been described and I pay more attention to clinical data, EBV-status of the lesion, transcription factors' status, and morphology (as long as it is of B-cell lineage) to arrive to final diagnosis.
ugnius 2008-06-28 10:26	Thank you. BOB1 and Oct2 are unavailable at the moment. EBER under construction. The B clonality will be checked. Add IH in progress. Add photos will be appended.
ugnius 2008-07-15 20:16	The last IH: CD79a+; LCA+; CD43-(not included).
tzankov 2008-07-16 18:51	CD79a supports the diagnosis of EBV+ LPD over Hodgkin lymphoma
hurwitz 2008-07-20 17:43	Most of us agree that the final diagnosis in this case is:     Age related EBV-associated LPD.     Thanks to the submitter and the contributors to the discussion
ugnius 2008-07-31 16:03	Please find POLYCLONAL results of PCR attached.
ugnius 2008-07-31 16:04	After EBER introduction in September I will be back with EBV status.
ugnius 2008-07-31 16:09	Appologies: MONOCLONAL KAPPA with polyclonal background.
hurwitz 2008-08-01 17:23	Thanks Ugnius for the information on the clonality, it will be interesting to see the EBER results
ugnius 2008-09-18 10:13	Please find a promised EBER (Hybridisation in situ, Ventana) positive result. It's the first EBER reaction in our centre.
hurwitz 2008-09-28 21:43	Congratulation to your first EBER1 ISH. My impression is that the staining is a bit too strong.
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