Myeloid Sarcoma of the Orbit and Ocular Adnexae

Myeloid sarcoma of the orbit and ocular adnexae (OMS) is a rare extramedullary manifestation of acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), and myeloproliferative neoplasms (MPNs). Currently there are no standard treatment guidelines for OMS.

On a retrospective review of the medical records, we identified 10 patients (pts) with OMS evaluated at our institution. We explored the pathologic, conventional cytogenetic and molecular cytogenetic features of these pts and analyzed their clinical features, treatments, and outcomes.

Among 10 acute leukemia pts with OMS, 6 (60%) were male; the median age of OMS onset was 49 yrs (range, 19 to 79). Morphological review of bone marrow (BM) aspirate smears and core biopsy specimens revealed treatment-related AML (t-AML) (n=4), AML with t(8;21) (q22;q22) (n=2), AML without maturation (n=1), AML with mutated NPM1 (n=1), CML-blast phase (n=1), and myeloperoxidase (MPO)-positive acute leukemia of ambiguous lineage (n=1). Monocytic or myelomonocytic differentiation was noted in 5 pts (50%). Conventional and/or FISH analyses performed on bone marrow in 10 pts demonstrated: +8 (n=3), t(8;21)(q22;q22) (n=2), −7 (n=2), del(7q) (n=2), t(1;3)(q21;q21) (n=1), t(2;11)(q14;q24) (n=1), t(10;11)(p13;q21) (n=1), diploid (n=2), and BCR/ABL1 rearrangement (n=1). Molecular genetic analysis, available in 8 cases, demonstrated NPM1 mutation (n=1) and NRAS mutation (n=1).

Ocular symptoms were the first sign of leukemia in 4 pts, 2 with concurrent BM disease. Of the 2 presenting with isolated OMS without BM disease, one developed BM disease 321 days after OMS, while the other remained without BM disease. Six pts developed OMS after the initial leukemia diagnosis: during disease progression before treatment initiation (n=1), during AML treatment of resistant disease (n=1), at relapse with concurrent BM relapse (n=2), or as the site of isolated relapse without concurrent BM involvement (n=2).

Clinical manifestations of OMS included: conjunctivitis, iris infiltration, lacrimal gland lesion, episcleritis, orbital mass, periorbital erythema or swelling, ocular secretions, ocular pain, visual problems, and/or retinal infiltrates. The diagnosis of OMS was confirmed by histologic and immunophenotypic analyses of biopsy specimens in the 8 pts from whom tissue could be obtained safely. Of the 2 pts who were not candidates for biopsy, 1 had a conjunctival lesion that involved the lacrimal gland and biopsy-confirmed skin and mediastinal disease. The second pt had intermittent bilateral blurred vision, with fundoscopically-visualized leukemic retinal infiltrates, intraretinal hemorrhages, and cotton wool spots. In both pts the ocular symptoms and lesions resolved with chemotherapy.

Treatment modalities included chemotherapy alone (n=3, including 2 who received intrathecal chemotherapy), chemotherapy and surgery (n=5), chemotherapy with focal radiation (XRT) (n=1), and XRT with surgery (n=1). Three pts underwent allogeneic stem cell transplantation (SCT) after OMS diagnosis.

In addition to OMS, 7 pts developed extramedullary disease in at least one other site, either concurrently with OMS or at other times during the disease course, including: CSF (n=1), breast (n=1), skin (n=3), lymph node (n=1), lung/mediastinum (n=2), and bone (n=1).

Two pts are in CR, 3 and 4 years after OMS diagnosis. Six died either of progressive leukemia or treatment complications. The median time from OMS diagnosis to death was 278 days (range, 39–779 days). Of the 6 pts who died, the OMS either improved or resolved with local or systemic treatment. Two pts have been lost to follow-up, 1 in CR 2 years after OMS diagnosis, and 1 with breast and BM relapse 10 months after OMS diagnosis.

OMS may be the initial sign of AML, with or without concurrent BM disease. OMS may also present as an isolated manifestation of relapse, without BM relapse. Extramedullary disease often develops in other sites during the disease course in AML pts with OMS. While OMS symptoms are non-specific, leukemic ocular involvement should be considered and a complete ocular exam is warranted. While t(8,21) is known to occur with extramedullary myeloid sarcoma and OMS, we also identified trisomy 8 in 30% of pts in our series.

No relevant conflicts of interest to declare.