The patient is a 79-year old woman who presented with a two week history of a rapidly growing mass in right maxilla. An oral examination demonstrated a firm, exophytic and painful lesion. It had a low signal intensity on the magnetic resonance imaging studies. An excisional biopsy was performed.
Histological sections show gingival mucosa with a deep and diffuse infiltrate of large atypical cells. The neoplastic cells have abundant cytoplasm, prominent nucleoli, vesicular chromatin and irregular nuclear contours. Many mitotic figures are present. Immunohistochemical stains demonstrate that the neoplastic cells are immunoreactive to CD45(+), CD43(+), CD4(+) and CD56(+). They are negative for other myeloid and monocytic markers (MPO, CD117, CD13 and CD68, CD163, respectively). Ki-67 proliferation index is increased at over 70%. The large cells are negative for B- and T- cell markers (CD20, CD79a, Pax-5 and CD2, CD5, CD3, CD8 stains, respectively). TdT is negative. Markers of the blastic plasmacytoid dendritic cells (CD123 and TCL-1) are negative.
A concurrent bone marrow biopsy and flow cytometric analysis revealed no evidence of a hematopoietic neoplasm. Notably, monocytes were increased in the peripheral blood (23.3%, normal values 1-11%).
DIAGNOSIS: MYELOID SARCOMA WITH MONOCYTIC/MONOBLASTIC FEATURES PRESENTING IN ORAL CAVITY
Myeloid sarcoma is a tumor comprised of immature granulocytic precursors, or myeloblasts that forms outside of the bone marrow. It is also referred to as chloroma, granulocytic sarcoma, and extramedullary myeloid tumor . It may or may not be associated with a concurrent medullary disease, and the 2008 WHO manual of Tumors of hematopoietic and lymphoid tissues classifies myeloid sarcoma it as a type of acute myeloid leukemia (AML) irrespective of the bone marrow and peripheral blood involvement. Some experts regard myeloid sarcoma as a type of AML presentation rather than its subtype. Rarely, myeloid sarcoma may be the first manifestation of acute leukemia, such as the aleukemic presentation in this patient. In patients in remission with previously treated disease, it may herald a relapse.
The most common sites of involvement include skin (leukemia cutis), head and neck, central nervous system, lymph nodes, and internal organs. When involving the head and neck region, myeloid sarcoma is more commonly seen in the soft tissues of orbit, nasal cavity and paranasal sinuses, while the jaws and lips are highly unusual sites. The intraoral occurrence is extremely rare with only a handful of case reports described in the literature. The demographic features of this case are also not characteristic as myeloid sarcoma usually arises in pediatric patients.
By definition, the term myeloid sarcoma is reserved for tumors that form mass-occupying lesions clinically rather than leukemic infiltrates that do not disrupt the normal architecture of the host tissue. Histologically, this correlates with a diffuse infiltrate of immature neoplastic cells forming sheets and nodules. The presence of admixed hematopoietic precursors of other lineages (erythroid, myelocytes and/or megakaryocytes) may be a useful clue to differentiate this process from certain lymphomas , such as lymphoblastic, Burkitt’s and a blastic variant of mantle cell lymphoma. However, the diagnosis hinges upon an accurate interpretation of a comprehensive flow cytometric and immunohistological markers.
Monocytic differentiation, such as seen in this case, is not uncommon. In fact, a monocyte-specific marker CD163 has high specificity for myeloid sarcoma. CD43 and CD68 are also often positive. An immature myeloid marker CD34 is positive in less than half of the cases, with CD117 being more commonly expressed. While B- and T-lineage specific markers are often negative, an aberrant expression of CD56 (such as in this case) can be seen. Cytogenetic work-up follows the same principles as AML involving the bone marrow.
Myeloid sarcoma portends a poor prognosis, and most patients succumb to the disease within months of diagnosis, despite the intensive chemotherapy treatment.
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