Case of the Month ...

Case History

A 65 year-old female with history of hypertension and hyperlipidemia started to experience cough. A chest X-ray revealed a left lower lobe pulmonary mass. She underwent a fine needle aspiration of the left lung nodule.

Diagnosis & Discussion
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Image Figs:

  • Figure 1: FNA smear, Diff-Quik stain, 400x

  • Figure 2: FNA smear, PAP stain, 400x

  • Figure 3: FNA smear, PAP stain, 100x

  • Figure 4: Cell block section, H&E stain, 200x

  • Figure 5: Cell block section, AE1/AE3 immunostain, 200x

  • Figure 6: Cell block, in situ hybridization for Epstein-Barr virus, 200x


  1. The cytological diagnosis of this left lung nodule aspirate is:
    1. Granulomatous inflammation and squamous metaplasia
    2. Small cell carcinoma
    3. Malignant lymphoma
    4. Lymphoepithelioma-like carcinoma
  2. The inflammatory infiltrate often associated with this tumor is composed predominantly of:
    1. Neutrophils
    2. Histiocytes
    3. Lymphocytes
    4. Mast cells
  3. This tumor has been associated with the presence of __________ in the atypical cells:
    1. Epstein-Barr virus
    2. Adenovirus
    3. Cytomegalovirus
    4. Herpes virus


    Lymphoepithelioma-like carcinoma (LELC) is an undifferentiated carcinoma with predominant lymphocytic infiltration. Initially described in the nasopharynx, these tumors can arise in a variety of sites including salivary glands, thymus, lung, stomach, skin, oral cavity, tonsil, larynx, trachea, hepatobiliary tract, bladder, uterine cervix, vagina, and vulva. LECL has classically been described to have a relation with Epstein Barr virus (EBV) in some organs. However, it is difficult to define if this association is related to racial or geographic influences rather than to the anatomic location of the tumor (1,2,3). The near-absence of EBV genome in LELC of the lung in the Western population suggests that EBV is not an important factor in its pathogenesis.

    LELC of the lung is an uncommon entity that was first reported in 1987 by Begin et al (4). Since then, approximately 150 cases have been reported in the literature (5). Lung LECL tends to affect younger non-smoking subjects of Asian descent predominantly. Histologically, the typical lung LELC consists of well circumscribed nodules characterized by nests, sheets, and cords of atypical cells in a syncytial-like growth pattern with prominent eosinophilic nucleoli, separated by thick fibrous bands containing large number of benign reactive lymphoplasmacytic cells and inflammatory cells. The stroma may show foreign body or tuberculoid granulomatous reaction, and occasionally, intramural amyloid globules with positive Congo red staining (5).

    The cytomorphologic features of lung LELC have been rarely described in the literature (6). The authors reported that smears were cellular with large sheets and small clusters of cohesive atypical cells. Some of the atypical cells can be spindle-shaped with an oval nuclei, fine chromatin and prominent nucleoli. Mild to moderate nuclear pleomorphism can also be seen. Admixed in the background are small lymphocytes, histiocytes and giant cells.

    Our case has similar cytologic features, however we also found areas of necrosis and epithelioid histiocytes forming granulomas. In the cell block preparation, syncytial sheets of atypical cells admixed with small lymphocytes could be found. Immunohistochemical studies were performed and the atypical cells were positive for TTF-1, AE1/AE3 and bcl-2. In situ hybridization for EBV RNA (EBER) was positive.

    We also performed electron microscopy (EM) on the surgical specimen obtained after the FNA diagnosis was rendered. EM confirmed the presence of clusters of round to oval squamous epithelial cells joined by small desmosomes. Their cytoplasm contained small bundles of tonofilaments and strands of rough endoplasmic reticulum. The nuclei were round with slightly irregular contours and exhibit one or two prominent nucleoli. Normal appearing small lymphocytes and dendritic cells (Langerhans cells) were intermixed with the tumor cells.

    The differential diagnosis of lung LELC on cytology would include metastasis from a nasopharyngeal LELC, granulomatous inflammatory diseases (tuberculosis), malignant lymphoma, melanoma, and metastatic sarcoma . A thorough ear, nose and throat (ENT) examination with biopsy if necessary can easily rule out a metastasis. In granulomatous infections, the epithelioid histiocytic cells would show negative immunostaining for epithelial markers, and positive staining for histiocytic markers (KP-1). Special stains for acid fast bacilli or Gomori Methanamine Silver stain, as well as microbiological correlation can also help differentiate between the two diagnoses. In Hodgkin and non-Hodgkin lymphomas, the tumor cells are more discohesive and would be negative for epithelial markers. Immunohistochemical studies can help differentiate between melanoma, sarcoma and LELC.

    The patient underwent an endoscopic ENT examination that ruled out a nasopharyngeal carcinoma before her surgery.


    1. d
    2. c
    3. a


  1. Castro CY, Ostrowski ML, Barrios R, Green L, Popper H, Powell S, Cagle PT, Ro JY. Relationship between Epstein-Barr virus and lymphepitheliom-like carcinoma of the lung: a clinicopathologic study of 6 cases and review of the literature. Human pathology 2001; 32(8): 863-872.

  2. Morbini P, Riboni R, Tomaselli S, Rossi A, Magrini U. EBER and LMP-1-expressing pulmonary lymphepithelioma-like carcinoma in a Caucasian patient. Human Pathology 2003 Jun; 34(6):623-5

  3. Chang YL, Wu CT, Shih JY, Lee YC. New aspects in clinicopathologic and oncogenes studies of 23 pulmonary lymphoepithelioma-like carcinomas. American Journal Surgical Pathology 2002 Jun; 26(6):715-23.

  4. Begin LR, Exkandari J, Joncas J, et al. Epstein-Barr virus related lymphoepithelioma-like carcinoma of the lung. Journal of Surgical Oncology 1987; 36:280-3.

  5. HO JC, Wong MP, Wah KL. Lymphoepithelioma-like carcinoma of the lung. Respirology 2006 (11): 539-545

  6. Chow LT, Chow WH, Tsui WM, Cahn SK, Lee JC. Fine-needle aspiration cytologic diagnosis of lymphoepithelioma-like carcinoma of the lung. Report of two cases with immunohistochemical study. American Journal of Clinical Pathology 1995 Jan; 103(1):35-40

Case contributed by
Stephanie Barak, M. D., David S. Schrump, M.D., Armando Filie, M.D.
National Cancer Institute
Bethesda MD 20892

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