1. 5th International Symposium October 22nd – 24th, 2015 - Varese, Italy
Russian Federal Research and Clinical Center of Pediatric Hematology Oncology and Immunology, Moscow, Russia
5th International Symposium
on Childhood, Adolescent and Young Adult Non-Hodgkin Lymphoma
October 22nd – 24th, Varese, Italy
Transformation of follicular lymphoma into diffuse large B-cell lymphoma in a 16 y.o. patient. Case report.
Abramov D.S.1,2 Konovalov D.M.1,2. Rogozhin D.V.2,1, Ponomarev N.I.2, Ol'shanskaya Y.V.1., Kazakova A.N1, Matveeva E.A1., Pshonkin A.V.1,2, Roshchin V.YU.1, Mitrofanova A.M.1,2 Kisliakov AN, 1.2, Myakova N.V.1
1 - Federal Research Center of Pediatric Hematology, Oncology and Immunology, named by Dmitry Rogachev, Moscow,Russia
2 - Russian Children's Clinical Hospital, Moscow, Russia
Background
Follicular lymphoma (FL) - a B-cell tumor from germinal centers of lymphoid follicles. It's main genetic component in 80% of cases is the translocation t (14;18)(q32; p21). FL is 20% of all malignant lymphoproliferative disorders, with median age of presentation 60 y. In children and adolescents only 2% accounted for the FL. Moreover, pedicatric FL differs from adults by good prognosis and the lack of the translocation t(14;18).Transformation of FL related to translocation of gene Myc, in more aggressive tumor, often diffuse large B-cell lymphoma, found in 25-30% of cases, leads to refractoriness and clinical progression.
H&E
CD3
CD20
BCL6
CD10
BCL2
Ki67
Fig.1 Morphological picture of follicular lymphoma grade 1-2. Multiple follicular structures presented with a mixture of large centroblasts. Follicles are presented CD20 positive B-lymphocytes, cells parafollicular zones CD3 positive T lymphocytes. Cells centers follicles have overexpression of CD10 and BCL6. Tumor cells were co-express BCL2 follicles and have a low level of expression of Ki67.
Case report
Patient T. 16 y.o., female, noticed increasing of right palatine tonsil,
treated symptomatically with a positive effect. А month later, she revealed enlargement of cervical lymph node . CT determined the enlargement
of intrathoracic, abdominal and retroperitoneal lymph nodes. Bone marrow biopsy showed follicular tumor infiltration (non show). Biopsy of a cervical lymph node, morphological, immunohistochemical and cytogenetic studies confirmed the diagnosis follicular lymphoma Grade 1-2, IV stage, risk group R3. She received 6 blocks of BFM-like chemotherapy and Rituximab with dramatic reduction of all lesions. But 2 months after the end of chemotherapy, CT revealed the tumor of the right ovary, 8x8 cm.  
Biopsy showed Diffuse large B-cell lymphoma. Tumor cells expressed CD20, BCL6, BCL2, Ki %. Chromosomal analysis detected the clone carrying simultaneously translocation t(14;18)(q32;q21) and t(8;14)(q24;q32), so called double hit lymphoma. FISH confirmed BCL2 gene rearrangement as part of the translocation t(14;18)(q32;q21) and restructuring of the gene C-MYC translocation as part of t (8;14)(q24;q32). BCL6 gene rearrangements were also found. She received second-line treatment (R-ICE) and allogeneic BMT, but further died due to the development of early tumor recurrence.
t(14;18)
BCL2
C-Myc
Fig. 2. Study of tumor cells by FISH,t(14;18), BCL2 b-a, but not C-Myc b-a.
t(14;18)
t(8;14)
t(t(14;18)
Fig. 3 Transformation FL to DLBCL with morphological signs of Burkitt's lymphoma. The tumor of the ovary. (HαE)
Fig 4. Cytogenetic karyotyping and FISH study of tumor cells sgowed
Conclusions
20-30% of follicular lymphoma cases, can transform into a more aggressive neoplasm with an extremely poor prognosis, and refractory to treatment. Only 2% of this lymphoma occurs in young adults and is was not described in the literature in children under 18 years.
Our presentation represents probably the first case of Grade 1-2 follicular lymphoma in a girl 16 y.o. with a typical morphological picture and the translocation t (14; 18), followed by transformation to diffuse large B-cell lymphoma with the restructuring of C-Myc gene as part of the translocation t (8;14).