Submitting Author: Adams, Julia Anne, MD
Institution: Indiana University School of Medicine
Additional authors:Magdalena Czader, MD, PhD
Session: Extramedullary manifestations of myeloid neoplasms

The patient is a 51-year old female with a history of chronic myelogenous leukemia, BCR-ABL1 positive initially diagnosed at the age of 49, who subsequently underwent matched related bone marrow transplant that same year. Two follow-up bone marrow exams 6 and 12 months after transplantation were negative for recurrent disease. The patient had been doing well until 20 months after transplantation when she presented with isolated tender right inguinal lymphadenopathy.

The patient underwent excision of a right inguinal lymph node. Grossly, the lymph node was enlarged (3.0 x 2.5 x 2.3 cm) and firm with a pale tan, fleshy, and focally hemorrhagic cut surface. Microscopic examination demonstrated complete effacement of the nodal architecture by sheets of variably sized blasts with round to oval nuclei, open chromatin, prominent nucleoli and relatively abundant cytoplasm. A proportion of blasts had large lobulated nuclei. Frequent dysplastic megakaryocytes with hypolobated and hyperchromatic nuclei were admixed. Scattered eosinophils and neutrophils were also noted.

Concurrent bone marrow exam (left posterior iliac crest) included biopsy, clot section and aspirate smear. The bone marrow was hypocellular and showed decreased trilineage hematopoiesis with M:E ratio of 3:1. Blasts were not increased and there was mild eosinophilia (differential count: 2% blasts, 2% promyelocytes, 8% myelocytes, 11% metamyelocytes, 10% bands, 23% neutrophils, 17% lymphoctyes, 2% monocytes, 6% eosinophils, and 19% nucleated red blood cells). Iron stain was positive. Loose clustering with few dysplastic megakaryocytes was focally seen on bone marrow biopsy.

Flow cytometric analysis of the lymph node demonstrated a population of leukemic blasts positive for CD34, HLA-DR, CD33, variable CD13, partial CD117, variable CD41 and CD61, with coexpression of CD7.

In addition to flow cytometry, select immunohistochemical stains were performed. Areas of blasts rich in dysplastic megakaryocytes were positive for megakaryocytic markers including CD61, Factor VIII, LAT, and partially for CD42b and CD34. These areas are negative for myeloperoxidase and CD117. Focally sheets of blasts and immature myeloid cells showed myeloperoxidase positivity. These areas are also weakly positive for CD117 and partially positive for CD34.

Flow cytometric analysis of the bone marrow demonstrated no evidence of myeloid malignancy. Immunophenotypically unremarkable T-cells and polyclonal B-cells were seen.

Lymph Node: 47XX,+8, t(9;22)(q34;q11.2), i(17)(q10)[20]

Concurrent Bone Marrow: 46,XX[50]

Not performed.

This case is an example of isolated extramedullary blast phase of chronic myelogenous leukemia in a patient in remission post hematopoietic stem cell transplantation. The immunophenotype indicated partial megakaryoblastic differentiation. Additional cytogenetic abnormalities seen in the lymph node involved by blastic proliferation included trisomy 8 and i(17)(q10). The concurrent bone marrow showed no morphologic, immunophenotypic or cytogenetic evidence of CML in chronic or blast phase.

Following the diagnosis of disease recurrence, the patient was started on Gleevec. She initially achieved complete remission; however she experienced multiple relapses with bone marrow involvement over the following two years. She then underwent salvage chemotherapy, which was complicated by profound polymicrobial sepsis and disease remission was not obtained. The patient died three years after the first blast phase.

We believe this case represents a rare case of extramedullary blast phase as the first manifestation of disease recurrence in a patient with a history of CML who underwent bone marrow transplantation.

Isolated extramedullary blast phase of previously diagnosed chronic myelogeneous leukemia, BCR-ABL1 positive.

Blast phase of chronic myelogenous leukemia, BCR-ABL1, involving inguinal lymph node with myeloid/megakaryocytic differentiation (myeloid sarcoma), status post bone marrow transplantation

Case 286