Megakaryocytes mimicking metastic breast carcinoma: A potential trap in the interpretation of sentinal lymph nodes

Archives of Pathology & Laboratory Medicine,  May 2002  by Hoda, Syed A,  Yusuf, Erika Resetkova Yasmin,  Cahan, Anthony,  Rosen, Paul P

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* False-positive diagnosis of lymph nodes occurs when a benign element in a lymph node, or in its capsule, is interpreted as metastatic carcinoma. This report describes a patient with breast carcinoma who had megakaryocytes in axillary sentinel lymph nodes mimicking metastatic carcinoma. The patient had no history of a hematologic disease, and we found no evidence of a concurrent hematopoietic disorder. The megakaryocytes were reactive for CD31, CD61, and von Willebrand factor, but not for cytokeratin (AEI/AE3). Megakaryocytes should be added to the list of benign histologic abnormalities that may simulate metastatic carcinoma in a sentinel lymph node.

(Arch Pathol Lab Med. 2002;126:618-620)

In recent years, sentinel lymph node (SLN) biopsy has emerged as an attractive option in the treatment of early breast carcinoma.1 The procedure is highly selective as a method for detecting the lymph node or nodes most likely to harbor metastatic carcinoma. Consequently, the staging of the axilla can be accomplished by this method without the morbidity of a full axillary dissection.

Sentinel lymph nodes are examined pathologically with multiple hematoxylin-eosin-stained sections and with cytokeratin immunohistochemistry. In most cases, the diagnosis of an SLN is uncomplicated. However, uncommon benign abnormalities in lymph nodes may be mistaken for metastatic carcinoma. These structures include nevus cell aggregates, benign (heterotopic) glands in the lymph node capsule, and multinucleated macrophages.2,3 Epithelial membrane antigen immunostaining of plasma cells and cytokeratin immunostaining of dendritic cells may also prompt a false-positive diagnosis .4,5 Herein, we report a case of breast carcinoma in which the presence of megakaryocytes in SLN mimicked metastatic carcinoma cells.

REPORT OF A CASE

A 35-year-old woman with a palpable mass in the right breast underwent a lumpectomy that showed a microinvasive carcinoma amid ductal carcinoma in situ of the comedo type. The latter involved the margins. Two weeks later, a right modified radical mastectomy was performed with a sentinel lymphadenectomy procedure. Tc99-labeled sulfur colloid and isosulfan blue were used to detect the SLN intraoperatively. Two SLNs were thus identified and excised. Biopsies of 2 additional lymph nodes in the same region were also performed. Frozen-section examination performed on both SLNs was negative for metastatic tumor. The right mastectomy specimen showed only minimal residual ductal carcinoma in situ. A prophylactic left simple mastectomy was performed at the same time and showed no significant histologic abnormality.

COMMENT

Megakaryocytes are normally present in the bone marrow and are only rarely detected in other organs in the absence of hematopoietic disease. The most frequent site for aberrant megakaryocytes is in the capillaries of the lungs. In this location, megakaryocytes are of no known diagnostic significance, except for possible misinterpretation as malignant cells.6,7

Megakaryocytes can be found in vascular channels of various organs, including the liver, the spleen, and in the parenchyma of lymph nodes, usually as a part of EMH. Misidentification of megakaryocytes as metastatic cancer in lymph node was reported by Weeks et al8 in a case of Wilms tumor. These megakaryocytes were present in the sinuses of a lymph node in the renal hilum and had been mistaken for metastatic tumor cells of the "anaplastic" type, thereby conferring "unfavorable histology" to the assessment of prognosis. With further study, it became apparent that these anaplastic cells had the cytologic and immunohistochemical characteristics of megakaryocytes.

The differential diagnosis of megakaryocytes in lymph nodes should include multinucleated histiocytes.3 Although both types of cells can be large, most histiocytes are comparatively larger and have more abundant cytoplasm than megakaryocytes. Macrophages contain multiple vesicular nuclei, in contrast to megakaryocytes. The latter generally contain multilobated nuclei. Immunostains are helpful for distinguishing megakaryocytes (nonreactive with CD68) from macrophages (reactive with CD68) and metastatic carcinoma (nonreactive with CD68, reactive with cytokeratin). Von Willebrand factor is considered to be the most reliable immunohistochemical marker for megakaryocytes.9 CD31 is immunoreactive with megakaryocytes, macrophages, Kupffer cells, osteoclasts, fibroblasts, and endothelial cells. CD61 is immunoreactive with megakaryocytes, myeloid progenitor cells, and endothelial cells. Immunoreactivity for both CD31 and CD61 is characteristic for megakaryocytes.9,10

There is usually histologic evidence of concurrent EMH on the rare occasions when megakaryocytes are present in lymph nodes. In such cases, the megakaryocytes are present in nodal sinusoids, and they tend to stand out from the adjacent nodal tissue because of their multilobated and hyperchromatic nuclei. It is these features that can mislead the unwary pathologist into rendering a diagnosis of metastatic carcinoma. Typically, megakaryocytes are the most conspicuous element on microscopic examination of EMH, although foci of erythropoiesis and developing granulocytes are also observed. As evident in our case, the difficulty may be compounded in rare instances by the absence of other precursor hematopoietic cells typically found at most sites of EMH.