Virchows Arch (2003) 443:695–699 DOI 10.1007/s00428-003-0879-y
LETTER TO THE EDITOR
Mattheos Bobos · Prodromos Hytiroglou · Georgios Karkavelas · Christos Papakonstantinou · Constantine S. Papadimitriou
Sialadenoma papilliferum of bronchus Received: 8 May 2003 / Accepted: 15 July 2003 / Published online: 21 August 2003 Springer-Verlag 2003
Sir, Salivary gland-type tumours of the bronchi include a variety of neoplasms with identical histological features to tumours of the major and minor salivary glands [4, 8, 9]. These lesions are uncommon and presumably arise from bronchial glands. Sialadenoma papilliferum (SP) is a rare tumour that has mostly been described in minor salivary glands of the mouth [3, 5]. In an extensive search of the literature, we have not found any mention of this neoplasm in the larynx, trachea or bronchi. We present a case of an endobronchial papillary tumour with histological and immunohistochemical features of SP. The patient was a 53-year-old man who was found to have a radiopaque lesion in the right lung on a routine Xray examination. The patient had a 40-year history of heavy smoking (40–60 cigarettes per day). He had noticed deterioration of the morning cough, accompanied by increased sputum production during the 4 months preceding admission. He also complained of dyspnea on exertion and mild weight loss. Chest radiographs showed a radiopaque lesion in the parahilar region of the lower lobe of the right lung (Fig. 1A). The cardiopulmonary index was within normal range. Bronchoscopy showed occlusion of the apical bronchus of the right lower lobe, which contained purulent and necrotic material. Cytological examination of a bronchial wash showed squamous cells without evidence of malignancy. Histological examination of a bronchial biopsy showed findings consistent with a benign papillary lesion. Computed tomoM. Bobos · P. Hytiroglou ()) · G. Karkavelas · C. S. Papadimitriou Department of Pathology, Aristotle University Medical School, 540 06 Thessaloniki, Greece e-mail:
[email protected] Tel.: +30-231-0999218 Fax: +30-231-0999229 C. Papakonstantinou Department of Cardiothoracic Surgery, Aristotle University Medical School, Thessaloniki, Greece
graphy (CT) scan of the chest revealed an area of bronchial thickening and consolidation accompanied by parenchymal changes suggestive of inflammation (Fig. 1B). Brain, abdominal and retroperitoneal CT scans, as well as bone nuclear scan, were normal. Pulmonary function tests included: – Forced vital capacity (FVC): 2.60 l/s (69% of predicted 3.79 l/s) – Peak expiratory flow rate: 3.74 l/s (47% of predicted 8.00 l/s) – Forced expiratory volume after 1 s: 1.38 l/s (45% of predicted 3.07 l/s) – Forced expiratory flow at 25–75% of FVC: 0.69 l/s (19% of predicted 3.62 l/s) These findings were consistent with moderate bronchial obstruction. Laboratory findings on admission included: hematocrit 44.3%, haemoglobin 15.1 g/dl, glucose 84 mg/dl, urea 36 mg/dl (normal 10–50 mg/dl), creatinine 0.74 mg/dl (normal 0.5–1.4 mg/dl), total protein 5.91 g/dl (normal 6.40–8.30 g/dl), albumin 3.60 g/dl (normal 3.40–4.80 g/ dl), globulin 2.31 g/dl (normal 3.00–5.00 g/dl), aspartate aminotransferase 18 U/l (normal 0–41 U/l), alanine aminotransferase 20 U/l (normal 0–38 U/l), serum lactate dehydrogenase 260 U/l (normal 0–480 U/l), prothrombin time 10.0/10.6 s, partial thromboplastin time 26.9/30.0 s and erythrocyte sedimentation rate 12 mm (1st hour). The patient underwent resection of the lower lobe of the right lung with dissection of paratracheal, interlobar and paraoesophageal lymph nodes. The patient is well 8 months after the operation, without evidence of recurrent tumour. The resected right lower pulmonary lobe measured 1495 cm and weighed 190 g. The lumen of the apical bronchus was occluded and moderately dilated by an exophytic papillary yellowish tumour mass, which measured 2.21.01.0 cm and was located 0.8 cm from the surgical resection margin (Fig. 1C). The surrounding area of pulmonary parenchyma, measuring 43 cm, showed marked consolidation. Serial sections through the lobe
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Fig. 1 Radiographic and gross pathological findings. A Plain chest X-ray showing a radiopaque lesion in the lower lobe of the right lung. B Computed tomography scan of the chest confirming the
revealed a second circumscribed roundish tumour nodule located 4.5 cm from the surgical resection margin. This was whitish in colour, firm in consistency and measured 1.8 cm in greatest dimension. Routinely stained sections of the papillary tumour showed complex papillary structures protruding into the bronchial lumen (Fig. 2A). The papillae were lined by a double row of cells, consisting of a luminal layer of nonciliated columnar epithelial cells and a basal layer of cuboidal myoepithelial cells (Fig. 2B). The epithelial cell nuclei showed mild pleomorphism without evident mitotic activity. In most areas, the epithelium was one to two cells in thickness; however, in multiple foci, epithelial tufts with thickness of several cells were present. Superficial portions of the papillae were lined by non-keratinizing stratified squamous epithelium (Fig. 2A). Inside the papillae, multiple gland- or duct-
presence of an area of consolidation. C Exophytic papillary lesion protruding at the cut surface of the apical bronchus of the right lower lobe
Fig. 2 Histological and immunohistochemical findings. A The tumour is composed of complex papillary structures filling the bronchial lumen. Metaplastic squamous epithelium is present in superficial portions of the papillae (left; original magnification 20). B The lining of the papillae consists of a double row of epithelial and myoepithelial cells. Focal tufting is present. Lymphoplasmacellular infiltrates are seen in the stroma (original magnification 200). C Gland-like structures containing eosinophilic material are seen inside the complex papillae (original magnification 100). D The deepest portion of the lesion is in continuity with bronchial glands (original magnification 100). E Both epithelial and myoepithelial cells are positive for cytokeratin 7 (upper left), whereas only myoepithelial cells are positive for cytokeratin 17 (upper right). Myoepithelial cells are positive for asmooth muscle actin (lower left); both epithelial and myoepithelial cells are positive for S-100 protein (lower right; original magnification 200)
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698 Table 1 Immunohistochemical findings in sialadenoma papilliferum of bronchus (comparison with bronchial glands and respiratory epithelium) Immunohistochemical stains
Sialadenoma papilliferum
Bronchial glands
Respiratory epithelium
Epithelium
Myoepithelium
Epithelium
Myoepithelium
Cytokeratin cam 5.2 Cytokeratin 7 Cytokeratin 17 Cytokeratin 19 Cytokeratin 20 EMA SMA S-100 protein GFAP
Positive Positive Rare positive foci Positive Negative Positive Negative Mostly positive Negative
Rare positive foci Focally positive Positive Positive Negative Negative Positive Mostly positive Focally positive
Positive Positive Negative Positive Negative Focally positive Negative Focally positive Negative
Focally positive Focally positive Positive Positive Negative Negative Positive Positive Negative
Positive Positive Focally positive in basal cells Positive Negative Positive Negative Negative Negative
Note: Abbreviations: EMA epithelial membrane antigen, SMA a-smooth muscle actin, GFAP glial fibrillary acidic protein
like structures were present; these were also lined by epithelial and myoepithelial cells. Most of these structures had irregular outlines, due to the presence of epithelial tufts and micropapillae protruding into the lumens (Fig. 2C). Some gland-like structures contained amorphous eosinophilic material. The stroma of the papillae consisted of fibrous tissue with moderate chronic inflammatory infiltrates, predominantly composed of lymphocytes and plasma cells. At the periphery of the lesion, the double-layered epithelium merged smoothly with the respiratory-type epithelium of the dilated bronchus. In one of the sections adjacent to the gland-like structures of the deepest part of the lesion, secretory units of mucinous and serous bronchial glands were present (Fig. 2D). The lung tissue distal to the tumour showed acute and chronic inflammation with fibrosis and alveolar remodelling. Sections of the smaller tumour showed poorly differentiated squamous cell carcinoma. Ten hilar, two paratracheal, two interlobar and five para-oesophageal lymph nodes were negative for metastatic tumour. Periodic acid-Schiff (PAS) stain of the papillary neoplasm showed focal apical staining in tumour epithelial cells, which was diastase resistant. The eosinophilic material present in gland-like structures was also PASpositive, diastase resistant. Immunohistochemical stains for various epithelial and myoepithelial markers were performed using the streptavidin-biotin-peroxidase complex method [7], in order to compare the features of the tumour cells with those of the bronchial glands and the respiratory epithelium. All antibodies were purchased from Dako (Glostrup, Denmark) with the exception of cytokeratin cam 5.2, which was obtained from Novocastra (Newcastle, U.K). The immunohistochemical findings are summarised in Table 1 and illustrated in Fig. 2E. SP has been reported in a variety of locations, including the palate, buccal mucosa, gingiva, tonsillar pillar, mandibular retromolar pad, lip, parotid gland and submandibular gland [2, 3, 5]. The pathological features of this neoplasm have been well described. SP is unique among salivary gland tumours because it manifests as an exophytic papillary excrescence of the mucosa rather than as a submucosal or intraglandular mass. A glandular proliferation is present immediately subjacent to the
papillary part of the tumour; this is composed of elongated and ectatic duct-like structures within the lamina propria, some of which may be cystically enlarged. Both ductal and papillary structures are lined by a double row of cells, including columnar epithelial and cuboidal myoepithelial cells. The superficial portions of the papillae are lined by stratified, presumably metaplastic, squamous epithelium [3]. The pathological features of our case were similar to those described in SP of other locations. The exophytic growth of the tumour resulted in obstruction of the bronchial lumen and bronchopneumonia. This clinically significant lesion was treated by lobectomy. The specimen was found to contain an incidental 1.8-cm squamous cell carcinoma, located away from the SP. Salivary gland-type tumours of the bronchi are uncommon and usually present as polypoid endobronchial lesions [4, 8]. The tumour types thus far reported in the literature include benign (mucus gland adenoma, myoepithelioma, oncocytoma, pleomorphic adenoma) and malignant (acinic cell carcinoma, adenoid cystic carcinoma, adenosquamous carcinoma with amyloid-like stroma, carcinoma ex pleomorphic adenoma, epithelial–myoepithelial carcinoma, mucoepidermoid carcinoma, sebaceous carcinoma) neoplasms [1, 4, 6, 9, 10, 11]. These lesions are believed to arise from bronchial glands and recapitulate the histological features of salivary gland tumours. In our case, the presence of focal continuity between bronchial glands and neoplastic structures strongly suggested such an origin. Furthermore, the immunohistochemical stains (Table 1) disclosed similar phenotypes in the epithelial and myoepithelial cells of the tumour and those of the bronchial glands. These histological and immunohistochemical features were sufficiently distinctive to rule out other salivary gland-type tumours, as well as the relatively common squamous papilloma of the tracheobronchial tree. In conclusion, we report a case of SP occurring in a large bronchus. Awareness of such rare lesions is important for pathologist and clinician alike, because such lesions may occasionally cause significant morbidity.
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