Submitting Author: Reddy, Vishnu VB, MD
Institution: University of Alabama at Birmingham (UAB)
Additional authors:Deniz Peker, MD, Sam Borak, MD, Dara Wakefield, MD
Session: Therapy-related myeloid neoplasms

This is a 51-year-old woman with a history of breast carcinoma diagnosed in 2010 (invasive ductal carcinoma with lobular features in the right breast) and underwent bilateral mastectomies, chemotherapy (taxol, Adriamycin and tamoxifen) and reconstruction. She recently (Nov 2012) complained of back pain. Imaging studies showed an L3 vertebral body lesion. An initial image-guided biopsy of this lesion was non-diagnostic, demonstrating only necrotic tumor and an open biopsy of L3 vertebra was performed.

Patient progressed to AML/M5 despite vigorous chemotherapy and passed away in April of 2013.

Open biopsy of L3 vertebra (Nov 2012)

Buffered formalin

12 separate biopsies (ranging from 0.2 – 2.1 cm are obtained. First 11 biopsies showed bone, fibrosis and necrotic tumor, the twelfth biopsy contained viable tumor cells. Microscopic examination demonstrates a dense infiltrate of pleomorphic large cells. These have enlarged, irregularly-shaped nuclei arranged as contiguous sheets of cells and some are dischohesive. Frequent and prominently enlarged nucleoli are identified in these cells. Similar atypical cells are also found in the attached blood clots. Normal marrow elements are not found. Initial microscopic impression was consistent with poorly differentiated carcinoma.

Immunohistochemical stains: Neoplastic cells are negative for S100, CK7, CK20, 34Be12, CAM 5.2, mammaglobin, CD79a, CD3, CD34, CD30, CD123, and CD117. Cells of interest are also negative for ER, PR and Her-2 not amplified.

Almost all neoplastic cells are strongly positive for CD43, myeloperoxidase (MPO), Vimentin (subsets), CD45 weak+, CD33 weak+. All controls are reactive.

Specimen submitted for flow was necrotic / noncontributory; however smear from flow sample showed rare large mononuclear cells.

None on the L3 specimen, later conventional karyotyping and FISH (MDS panel and AML) on bone marrow and peripheral blood were negative

Molecular studies are performed on fixed formalin L3 tissue (MD Anderson). FISH for Abbott MLL probe was negative. FISH for Abbott ETO/AML1 was negative for translocation, but was positive for an extra copy of ETO (RUNX1T1).

Later conventional cytogenetic studies on the bone marrow and peripheral blood were negative. An extended FISH AML and MDS panel on the blood and bone marrow was also negative.

Initial clinical, imaging and cytology findings were all strongly suggestive of metastatic carcinoma. Later biopsy morphology and IHC stains supported myeloid sarcoma/tumor confined only to the L3 vertebra.

Two later staging bone marrow biopsies were negative for leukemic infiltrates. However rare circulating blasts noted on blood smears. Conventional cytogenetic studies on the bone marrow and peripheral blood were negative. An extended FISH AML and MDS panel on the blood and bone marrow was also negative.

This case illustrates the myeloid sarcoma (post chemo secondary malignancy) can very easily mimic metastatic carcinoma and it is impartment to perform immunohistochemical stains and molecular studies for correct diagnosis and appropriate treatment. In addition this is a somewhat unusually rapid presentation of secondary myeloid sarcoma - within 2 years of chemotherapy for breast carcinoma.

Ref:

1. Klco JM et al. State of the art in myeloid sarcoma. Int J Hematol. 2011;33(6):555-65

2. Amador-Ortiz C et al. Use of novel immunohistochemical markers in the diagnosis of cutaneous myeloid sarcoma. J. Cutan patho. 2011;38(12):945-53.

Myeloid sarcoma, post chemotherapy related, confined only to L3 vertebral body.

Myelomonocytic blasts, CD43+, MPO+, CD33 weak+, D45 weak+

Therapy-related myeloid neoplasm, myeloid sarcoma (myelomonocytic)

Case 58