Extramedullary leukemic deposits often have to be differentiated clinically from infections and carcinomas for which FNAC is an important diagnostic tool. There are only a few studies describing the morphological features of acute leukemia on FNA smears, most of them being case reports.[5
] However, of these, only one report discusses in detail the cytological features indicative of megakaryoblastic differentiation.[5
] We report the morphological features in a case of AML M7 with involvement of cervical lymphnode and cerebrospinal fluid. On FNAC, granulocytic sarcomas can be classified into blastic, immature, and maturing forms of leukemias, based on the proportion of blasts to the more differentiating granulocytic cells.[20
Blasts from AML M7 typically show more abundant cytoplasm with a relatively lower nuclear to cytoplasmic ratio than what is seen in other subtypes of leukemia. In addition, they show granular cytoplasm and cytoplasmic blebbing.[5
] Presence of blasts of varying sizes including both small and large blasts, focal clumping of blasts forming small groups may also indicate the possibility of megakaryocytic differentiation. Micromegakaryocytes in the form of large cells with single but multilobated nuclei, and/or bi or multinucleated cells having dusky cytoplasm or megakaryocytes along with dispersed giant platelets in the background may also be seen.
Although monoblasts also show nuclear membrane folds and indentations along with scant to moderate cytoplasm similar to megakaryocytes,[18
] they lack other features like multinucleation, multilobation, cytoplasmic shredding, micromegakaryocytes, and giant platelets. Promyelocytes and promyeloblasts also show nuclear convolutions and low nucleo-cytoplasmic ratio, although some might have Auer rods. Kumar PV described many faggot cells (promyelocytes showing many Auer rods) in a case of granulocytic sarcoma diagnosed by FNAC.[7
] Auer rods are however not seen in cases of AML M7. In the study by Suh et al
, Auer rods were not seen in any of 27 cases of granulocytic sarcomas included in their study.[22
] Another common differential is extramedullary hematopoiesis, especially when a deposit is characterized by presence of more maturing myeloid forms. A clinical history of myeloproliferative disorder or myelophthisic anemia, the presence of cells of erythroid lineage and also myeloid precursors besides megakaryoblasts can aid in making a correct diagnosis.[22
] Metastatic carcinoma, when poorly differentiated, is an important differential diagnosis for AML M7 due to the presence of grouping of blasts, more abundant cytoplasm and large size of the blasts. Poorly differentiated carcinoma may, however, have a suggestive clinical history. Additionally, the tumor cells in carcinoma have coarser chromatin are more monomorphic and are cytokeratin positive on immunocytochemistry. Multinucleated giant cells, if present, will have more bizarre hyperchromatic nuclei with or without prominent nucleoli in contrast to megakaryoblasts. In the case under discussion since there was a history of a mediastinal germ cell tumor, metastasis from the same may also be considered as a differential both clinically as well as on morphological assessment. Of the germ cell tumors, seminoma especially shares some morphological features with leukemia/lymphoma infiltration as it is characterized by a hypercellular cytologic preparation with cells dispersed singly as well as in loosely dyscohesive clusters. The cells have scant to moderate occasionally vacuolated cytoplasm. Nuclei are round to oval with thin nuclear membrane, vesicular chromatin, and prominent one central nucleolus or two to three smaller nucleoli. Due to cytoplasmic fragility, bare nuclei are common place. However, the cells do not show cytoplasmic pseudopod formation. In contrast to megakaryoblastic leukemia which shows a more polymorphic population of cells of variable sizes with multinucleation and multilobation, multinucleated cells are usually absent in seminoma except for occasional “syncytiotrophoblast-like” cells. Also background in the latter may have necrotic debris along with variable numbers of lymphocytes, plasma cells, and epithelioid histiocytes. A characteristic “tigroid” background may be noted on Romanowsky stains.[23
] In comparison, AML M7 is more typified by presence of giant platelets and cytoplasmic fragments. Epithelioid histiocytes have not been typically associated with AML M7. However, some cases may be difficult to further characterize, in which case immunocytochemistry may be used. Seminoma cells are immunopositive for CD117, placental-like alkaline phosphatase (PLAP), and sometimes for cytokeratin, all of which are negative in a case of megakaryoblastic leukemia except for CD117 which may be focally positive. Embryonal carcinoma and choriocarcinoma usually do not share overlapping morphological features with leukemia. Smears in the former show mitotically active, markedly atypical cells arranged as glandular and papillary 3-dimensional structures.[24
] Aspirates from choriocarcinoma show an admixture of multinucleated syncytiotrophoblasts and the mononuclear cytotrophoblasts in a background of hemorrhage and necrosis.[24
] Although syncytiotrophoblasts may be misinterpreted for megakaryoblasts, they are much larger with more abundant cytoplasm, several pleomorphic nuclei and lack nuclear lobations. A metastatic malignant melanoma is a common differential for any undifferentiated malignancy. The tumor cells are mostly epithelioid-cell type, dispersed singly, having abundant cytoplasm; marked anisokaryosis, bi- and multinucleation are common. Nuclei are usually eccentrically placed and have prominent nucleoli. An important point of distinction is the presence of intranuclear pseudo-inclusions. Cytoplasmic melanin pigment, present only in a minority, is beyond doubt the most diagnostic. Confirmation in a case of amelanotic melanoma may be done with the aid of monoclonal antibodies for S-100 and HMB-45.[25
] In morphologically ambiguous cases, a panel of antibodies including LCA, MPO, CD33, CD34, CD61, CD43, TdT, factor VIII, CD117, PLAP, S-100, HMB-45, and cytokeratin should help in arriving at the diagnosis.[26
] Blasts in the present case were positive for CD 61 and CD34. Suh and coauthors have used flow cytometry on their FNA material to characterize their cases of granulocytic sarcomas.[22
] Farray et al
. also have described a case of megakaryoblastic leukemia involving pleural cavity; they did not give detailed morphological description of the blasts though they performed a flow cytometry on pleural effusion fluid.[6
In the cerebrospinal fluid sample evaluated in the present case, blasts, micromegakaryocytes and cells resembling megakaryocytes could all be identified as seen in the aspiration smears.
This is the first report describing the finer cytomorphological features suggestive of megakaryoblastic differentiation on both aspiration and effusion smears. The features highlighted here may be of help in diagnosis and subtyping of extramedullary leukemic deposits of AML M7, especially in the event of a dry bone marrow tap, which is a common problem.