Pulmonary well‐differentiated fetal adenocarcinoma diagnosed by bronchial brush and immunocytochemistry

Dear Dr. Bedrossian: A 41-yr-old man with a long history of cigarette smoking presented to his family physician with an intermittent cough of 4-wk duration. Physical examination revealed no remarkable findings. A chest roentgenogram showed a 3-cm mass lesion located near the hilum of his right lung. A chest CT-scan confirmed the lesion to be a well-demarcated and solid tumor located in the lobar bronchus of the right middle lobe. No hilar lymphadenopathy was identified. The patient underwent a bronchoscopy, and a tumor involving the lobar bronchus of the right middle lobe was visualized. A cell sample was obtained by bronchial wash, and the bronchial lesion was brushed two times. Four direct smears prepared from two bronchial brushes and four cytospin smears prepared from the bronchial wash were fixed in 95% ethanol and stained with Papanicolaou method. Two tumor tissue fragments measuring 3 mm in greatest dimension obtained by biopsy were fixed in formalin and processed for routine histologic examination. The bronchial wash was negative for malignant cells. The four smears prepared from two bronchial brushes were cellular and revealed irregular, monolayered sheets of malignant epithelial cells showing clear, ill-defined cytoplasm, slightly pleomorphic, round or oval nuclei and inconspicuous nucleoli. In a few tumor cell groups nuclear crowding and overlapping were noted. The cytologic findings were in keeping with an adenocarcinoma with clear cell change (Fig. 1). However, a pulmonary welldifferentiated fetal adenocarcinoma (WFA) was not ruled out with certainty. Two Papanicolaou-stained smears containing tumor cells were stained with periodic acid-Schiff (PAS) and with PAS with prior diastase digestion (PASD). The tumor cell cytoplasm reacted positively with PAS and negatively with PASD, indicating a nonmucus secreting adenocarcinoma that was rich in glycogen contents. One Papanicolaou-stained smear was stained with commercial chromogranin antibody by the avidin–biotin-complex (ABC) technique without prior destaining. The tumor cells that were present reacted positively with this antibody. The cytologic, cytochemical, and immunocytochemical features of the patient’s tumor were in keeping with a pulmonary WFA. The two biopsied tumor tissue fragments showed severe crushing artifacts and were nondiagnostic. The patient’s lung tumor was subsequently removed by right pneumonectomy. The resected right lung showed a round, solid malignant tumor arising from the middle lobe lobar bronchus with minimal invasion into the surrounding lung parenchyma. Several tumor tissue blocks were fixed in formalin and processed for histologic, histochemical, and immunohistochemical studies. Histologically, the lung tumor consisted of branching tubules lined by a single layer of columnar epithelial cells with clear cytoplasm, basally located, oval, slightly pleomorphic, hyperchromatic nuclei and inconspicuous nucleoli (Fig. 2). In most tumor cells a large supranuclear cytoplasmic clear vacuole was present. The stroma contained capillary blood vessels and scattered benign spindle-shaped fibroblastic cells, and no malignant stromal cells were noted. Five-micron-thick sections from a representative tumor tissue block were stained with PAS, PASD, and with commercial antibodies against neuron-specific enolase and chromogranin by the ABC method. The tumor cell cytoplasm stained positively with PAS and with neuron-specific enolase and chromogranin antibodies, and negatively with PASD, suggesting a nonmucus secreting adenocarcinoma with high glycogen con*Correspondence to: Gia-Khanh Nguyen, M.D., Division of Anatomical Pathology, University of Alberta Hospitals, 8440-112 Street, Edmonton, Alberta, Canada T6G 2B7. E-mail: knguyen@cha.ab. ca DOI 10.1002/dc.20409 Published online in Wiley InterScience (www.interscience.wiley.com).