Case Workshop of Society for Hematopathology and European Association for Haematopathology
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1 Case Workshop of Society for Hematopathology and European Association for Haematopathology Aliyah Rahemtullah 1, Martin K Selig 1, Paola Dal Cin 2 and Robert P Hasserjian 1 Departments of Pathology, 1 Massachusetts General Hospital and 2 Brigham and Women s Hospital, Boston, MA
2 Clinical History 25-year-old woman from Belarus who developed painless enlargement of her right submandibular gland accompanied by sore throat Otherwise asymptomatic History of Chernobyl radiation exposure at age 6 No prior history of malignancy Dentist referred her to an ENT surgeon
3 Clinical History-2 Neck CT scan revealed enlarged right submandibular gland, submental lymph nodes, and jugular lymph nodes FNA of right submandibular gland on 6/12/06 was non-diagnostic Excision of right submandibular gland was performed on 8/2/06 Mass had enlarged from 1.5 cm to 5.0 cm in the interim
4 Pathology 5 cm lobulated, tan, firm mass replaced the right submandibular gland and extended into adjacent submental lymph node Frozen section diagnosis: Dense lymphoid infiltrate No evidence of salivary glandular malignancy Lymphoma work-up performed (touch preparations and flow cytometry)
5 Submandibular gland
6 Submandibular gland
7 Submandibular gland
8 Flow Cytometry
9 CD34 CD117 MPO lysozyme CD68 CD43
10 Diagnosis Myeloid sarcoma involving salivary gland and partially involving submental lymph node Presence of eosinophils and eosinophil precursors raised the possibility of AML with inv(16) No fresh tissue was sent for karyotyping Interphase FISH was performed on touch preparations and paraffin-embedded tissue Probes for 5q and 7q deletion Probes for BCR-ABL, MLL, CBFB, PML-RARA, AML1-ETO rearrangement
11 Separation of 5 and 3 probes to CBFB in 31/55 nuclei
12 Laboratory Studies CBC WBC: 7,700/mm 3 Hemoglobin: 14.4 g/dl Platelets: 291,000/mm 3 Differential Neutrophils: 74% Lymphocytes: 19% Monocytes: 4% Eosinophils: 2% Basophils: 1% Electrolytes and LDH within normal limits
13 Results of bone marrow examination Normocellular marrow with trilineage maturing hematopoiesis Aspirate differential normal (1% blasts) Flow cytometry: 1% blasts Cells with similar phenotype to the submandibular gland blasts were not detected Cytogenetics: 46, XX [20]
14 Bone marrow biopsy (8/7/06)
15 8/12/06 Additional Testing with PET Abnormal FDG uptake in right neck, left breast and right internal mammary LNs
16 Left Breast biopsy (8/14/06)
17 Diagnosis AML with inv(16) Presenting as myeloid sarcoma of the submandibular gland and breast without bone marrow involvement
18 Myeloid Sarcoma (1) May occur concurrently with (35%) or following (38%) a diagnosis of AML that involves bone marrow 27% present de novo without concurrent bone marrow involvement Most common sites of presentation: Skin (28%), lymph node (16%), testis (7%), intestine (7%), also bone, soft tissues, orbit, mediastinum, uterus, ovary <1% present in breast or salivary gland Often initially misdiagnosed as NHL Yamauchi et al. Cancer 2002;94:1739 Pileri et al. Leukemia 2007;21:340
19 Myeloid Sarcoma (2) Most common genetic abnormalities (FISH) +8, -7, 5q- (~25%) MLL (9%) inv(16) (5%) Plasmacytoid monocyte foci observed in 3/4 cases (all involving intestine) Both leukemic blasts and plasmacytoid monocytes shared inv(16) by FISH analysis t(8;21) is more common in de novo myeloid sarcomas and in children NPMc+ (14%) Local therapy is inadequate Considered high-risk AML with poor prognosis Pileri et al. Leukemia 2007;21:340 Falini et al. Leukemia 2007;21:1566
20 Is this a radiationrelated leukemia?
21 Leukemia After Chernobyl Increased leukemia risk well-documented after ionizing radiation (atomic bomb, occupational, therapeutic) Typically occurs 2-5 years after exposure Several studies have failed to demonstrate an increased leukemia risk in children exposed to Chernobyl radiation May have been underpowered to detect small changes in rates of rare diseases such as leukemia One case control study suggests possible increase in the Ukraine Parkin et al. Br J Cancer 1996;73:1006 Cardis et al. J Radiol Prot 2006;26:127 Noschenko et al. Int J Cancer 2002;99:609
22 Follow-up The patient received standard AML induction chemotherapy with daunorubicin and cytarabine Breast mass regressed in the 14 days following induction Biopsy of site of previous breast mass confirmed no evidence of leukemic infiltrate 14 days post induction therapy 3 cycles of consolidation with high dose cytarabine Patient remains in apparent remission 14 months after diagnosis
23 Issues Raised By This Case (1) How should myeloid sarcoma disease be followed in the absence of bone marrow involvement? Day 14 breast biopsy in lieu of day 14 bone marrow sample Serial PET scans Bone marrow sampling repeated 5 and 14 months post-therapy (both negative)
24 Follow-up PET scan 8/12/06 10/4/07
25 Issues Raised By This Case (2) Does this patient need an allogeneic stem-cell transplant? Good prognosis conferred by inv(16) abnormality, but extramedullary disease is poor prognostic feature No suitable donor has been identified No current plans for allo-sct, but peripheral blood stem cells have been collected for possible auto-sct should disease recur
26 Probability of Survival for AML with t(8;21) Patients Byrd et al. JCO 1997;15:466
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