-

-

-

19 yrs

M

+

+

+ Few reddish skin nodules 5-7 mm in diameter

+ A tumor-forming mass located in temporal lobe of brain at post-transplant relapse.

17

9.0

296

No blasts.

Bone marrow smears showed hypercellular bone marrow with 54.4% blasts. They were negative for myeloperoxidase, whereas most of them positive for PAS stain. The cytoplasm of blasts was narrow and basophilic. Blasts had rounded nucleus and finely dispersed chromatin with well-contoured nucleoli. Erythropoiesis and myelopoiesis were decreased. Erythropoiesis had signs of megaloblastosis. Megakaryocytopoiesis: hypolobular and polyploid megakaryocytes.

B-ALL

Positive for CD34, CD10, CD19, CD20, CD38.

Not performed.

Histopathology of the skin nodules was remarkable for interstitially located groups of small- and middle-sized lymphoid blast-like cells, which were positive for TdT, PAX-5, CD20, CD10, negative for T-cell and myeloid markers and had a very high proliferation rate (Ki-67 index above 90 %). C-myc oncogene product was additionally assessed with immunohistochemistry (clone Y69). Over 90% of blast cells in the skin appeared to be positive for ?-myc, although staining pattern was markedly heterogeneous. The brain tissue (at post-transplant relapse) contained a dense cellular infiltrate composed of middle-sized PAS-positive blasts with oval or round nuclei, containing 2-3 small nucleoli. Tumor cells were uniformly positive for TdT, CD19, PAX-5, and CD79a and had a very high Ki-67 proliferation index. C-myc oncogene product was demonstrated in over 85% of cells with heterogeneous staining pattern, compatible with indirect c-myc up-regulation.

Not performed.

Common acute lymphoblastic leukemia.

09-2012

Treatment was started according to ALL-2009 protocol, containing Daunorubicin, VIncristine and L-asparaginase. CNS prophylaxis therapy consisted intrathecal treatment, whereas cranial irradiation was not used.

+ Complete remission was achieved on 11/2012

-

+ Complex medullar and CNS extramedullary relapses were diagnosed repeatedly on 10 and 13 months after remission. The patient received allogeneic HSCT on 04/2014. Complete remission was achieved on 06/2014. Isolated post-transplant CNS relapse was diagnosed on 11/2014.

Positive for CD34, CD10, CD19, CD20, CD38.

D

29

Bone marrow aspirate, brain tumor mass (by stereotactic brain biopsy at post-transplant relapse).

24 without stimulating agents.

GTG

45,Y,der(X)t(X;8)(q28;q11.2)[20]

45,Y,der(X)t(X;8)(q28;q11.2)[20]

Fluorescence in situ hybridisation (FISH) with whole painting probes for 8 and X chromosomes (Metasystems, Germany). Multicolor banding, using a multicolor probe for chromosome 8 (Metasystems, Germany).

The unbalanced translocation der(X)t(X;8)(q28;q11.2) was revealed in all metaphases.

RT-PCR

Leukemic cells were negative for t(1;19)E2A-PBX1, del(1)SIL-TAL1, t(12;21) TEL-AML1, and t(9;22) BCR-ABL.

Identical chromosome abnormalities in leukemic cells at diagnosis and in the cells from brain tumor-forming relapse support the origin of both from common leukemic clone. c-Myc is one of the genes located on 8q which may be implicated in disease biology. Immunohistochemical staining for c-myc protein showed positivity of >85% of leukemic cells (at disease onset and at relapse), although with markedly heterogeneous staining pattern, compatible with indirect c-myc up-regulation. The latter, in turn, could increase proliferative potential of leukemic cells as well as their resistance to chemotherapy. Finally, trisomy 8 in ALL patients is considered to be indicative of poor prognosis [Garipidou et al, 1990].

MD, PhD Tatiana Gindina, Cytogenetics Laboratory; R.M. Gorbacheva Research Institute of Pediatric Oncology, Hematology and Transplantation at First Saint-Petersburg State Medical University named I.P.Pavlov, Russia; Leo Tolstoi Str., 6/8, Saint-Petersburg, Russia, 197022 Tel/Fax: + 7 (812) 338-62-65