Arch Pathol Lab Med—Vol 128, December 2004 Leukemoid Reaction: A Diagnostic Clue—Mukhopadhyay et al 1445 Leukemoid Reaction A Diagnostic Clue in Metastatic Carcinoma Mimicking Classic Hodgkin Lymphoma Sanjay Mukhopadhyay, MD; Surabhi Mukhopadhyay, MD; Katalin Banki, MD; Shirish Mahajan, MD ● We report on 2 patients who were initially suspected to have classic Hodgkin lymphoma because of lymphadenop- athy and the presence of Reed-Sternberg–like cells. Both patients had an associated leukemoid reaction (using a threshold leukocyte count of 50 000/L) and were even- tually diagnosed with metastatic carcinoma. Disseminated carcinoma can mimic Hodgkin lymphoma clinically, radio- logically, and histologically. Reed-Sternberg–like cells may be found in carcinomas, and they represent a particularly challenging diagnostic pitfall for the unwary. When these cells lead to a suspicion of Hodgkin lymphoma, the pres- ence of a leukemoid reaction should prompt the patholo- gist to question the diagnosis. Misdiagnosis can be avoided by the use of cytokeratin whenever a leukemoid reaction is present in a suspected case of Hodgkin lymphoma. (Arch Pathol Lab Med. 2004;128:1445–1447) R eed-Sternberg (RS) cells, when found on a background of lymphocytes, plasma cells, and eosinophils, sug- gest a diagnosis of classic Hodgkin lymphoma. However, RS-like cells can be seen in carcinomas and can lead to misdiagnosis. Leukemoid reactions (using a threshold leu- kocyte count of 50 000/L) are relatively far more likely to be encountered in the setting of metastatic carcinoma rather than in Hodgkin lymphoma. We report here on 2 patients with leukemoid reactions in a setting of dissem- inated malignancy. The presence of RS-like cells histolog- ically led to an initial impression of Hodgkin lymphoma, but both patients were eventually diagnosed as having metastatic carcinomas. REPORT OF CASES Case 1 A 78-year-old man presented with cough, shortness of breath, and weight loss for several months. Radiologic investigations re- vealed a 5-cm right lung mass with enlarged hilar and medias- tinal lymph nodes. Cytologic examination of brushings obtained Accepted for publication August 16, 2004. From the Departments of Pathology (Drs Sanjay Mukhopadhyay and Banki) and Medicine (Drs Surabhi Mukhopadhyay and Mahajan), State University of NewYork Upstate Medical University, Syracuse. The authors have no relevant financial interest in the products or companies described in this article. Reprints: Sanjay Mukhopadhyay, MD, Department of Pathology, State University of New York Upstate Medical University, 750 E Adams St, Syracuse, NY 13210 (e-mail: mukhopas@upstate.edu). at bronchoscopy revealed RS cells (Figure 1), suspicious for clas- sic Hodgkin lymphoma. Staging for Hodgkin lymphoma was performed. Complete blood count at diagnosis revealed a total leukocyte count of 52000/L, with 92% neutrophils, 3% bands, 4% lymphocytes, and 1% monocytes. There was no middle bulge or basophilia. Bone marrow biopsy revealed a hypercellular mar- row with no evidence of malignancy. The hematologic picture was suggestive of a leukemoid reaction. Computed tomographic scan of the abdomen showed bilateral 5-cm hypodense adrenal masses lacking contrast enhancement (Figure 2). The patient de- veloped superior vena cava syndrome for which radiotherapy was planned. In view of the need for a definitive diagnosis prior to radiotherapy, a bronchoscopic biopsy was performed, which showed a non–small cell carcinoma with RS-like cells. The atyp- ical cells stained positively for cytokeratin (CK) and negatively for CD15 and CD30. The diagnosis was revised to carcinoma of the lung with metastases to the adrenals. The patient died 4 weeks after diagnosis despite treatment with carboplatin, pacli- taxel, and radiation therapy. Case 2 A 37-year-old man presented with worsening abdominal pain and a 50-pound weight loss during a 3-month period. Exami- nation revealed left posterior cervical lymphadenopathy and he- patomegaly. Complete blood count at diagnosis revealed a total leukocyte count of 50000/L, with 94% neutrophils and without a middle bulge or basophilia, which is consistent with a leuke- moid reaction. Computed tomographic scans of the abdomen re- vealed a right-sided abdominal mass, which appeared to be aris- ing from the kidney, with involvement of the retroperitoneal lymph nodes (Figure 3). The clinicoradiologic differential diag- nosis was lymphoma versus metastatic carcinoma. Excision bi- opsy of cervical lymph nodes showed extensive infiltration by dyscohesive sheets of large RS-like cells (Figure 4). The back- ground consisted of neutrophils and occasional plasma cells. The histologic picture was considered suspicious for classic Hodgkin lymphoma. However, immunohistochemical stains showed the RS-like cells to be positive for pan-CK, CK CAM 5.2, and CK AE1/AE3 (focal). The cells were negative for leukocyte common antigen, CD20, CD3, CD30, and CD15. A diagnosis of metastatic carcinoma was made. The results of additional immunostains (CK7 and CK20 negative, vimentin positive) suggested a renal primary. The patient developed painful scrotal swelling, which was thought to be caused by progressive retroperitoneal adenop- athy. Radiotherapy was administered to the retroperitoneum. De- spite therapy with paclitaxel and carboplatin, the patient died 6 weeks after diagnosis. COMMENT The presence of RS-like cells in several conditions other than classic Hodgkin lymphoma is well documented in the literature. 1–4 These conditions include several subtypes