Image1: Bronchial washing- Bronchoalveolar cell carcinoma - Cluster of regular epithelial cells (embryo-shaped).

Image2: Sputum- Bronchoalveolar cell carcinoma -Three dimensional cluster of epithelial cells

1. An uncommon tumor which may exfoliate profusely in sputum and lavage samples.

2. Multiple three-dimensional groups of small to medium sized cells with papillary or “embryo-shaped” forms.

3. Cyanophilic cytoplasm, vacuolated in some cases, but with no cilia.

4. Rounded nuclei, with granular chromatin and visible nucleoli, difficult to view in the center of clusters.

5. Necrosis is not usually seen.

6. Correlation with radiological findings of diffuse shadowing is important.

Cytomorphologic criteria of bronchioloalveolar cell cancer.Pneumologie. 1990 Feb;44 Suppl 1:610-1.

Cytological material obtained from 100 patients with histologically proven bronchiolo-alveolar cell carcinoma was evaluated on the basis of 27 criteria. Particular features observed were a monocytoid nuclear delimitation (98.4%), central position of the nucleus (90.2%), light-coloured nuclear sap (52.5%), double-nucleation (98.4%), multinucleation (72.1%), phagocytosis (55.7%). Of the features of the accompanying reaction, psuedoproteinosis (9.8%), the presence of hyperplastic pneumocytes II (75.4%) and psammoma bodies (1.6%) are worthy of mention.

Misclassification of bronchioloalveolar carcinoma with cytologic diagnosis of lung cancer.J Thorac Oncol. 2006 Nov;1(9):943-8.

INTRODUCTION: Cytology is commonly used to diagnose non-small cell lung cancer (NSCLC) but is an inaccurate means of diagnosis of bronchioloalveolar carcinoma (BAC). The aims of this study were to calculate the sensitivity and specificity of cytologic diagnosis of BAC and to estimate the misclassification of BAC as other subtypes of NSCLC. METHODS: Preoperative fine-needle aspiration cytology diagnoses were compared to histology diagnoses in 222 patients, including 51 patients with pure or mixed BAC, who underwent lung resection for NSCLC at our institution since 1999. RESULTS: The sensitivity and specificity of a cytologic diagnosis of BAC were 12% and 99%, respectively. Based on cytologic diagnosis, 63% of BAC was misclassified as adenocarcinoma, and 18% was misclassified as undifferentiated NSCLC. In this cohort, 35% of adenocarcinomas and 12% of undifferentiated NSCLC diagnosed by cytology had BAC histology. CONCLUSIONS: Diagnosis of NSCLC by cytology alone results in significant misclassification of BAC, most commonly as adenocarcinoma or undifferentiated NSCLC. Because patients with BAC respond differently to certain treatments such as endothelial growth factor receptor inhibitors and surgical resection of multifocal lung cancer, misclassification of BAC may have important therapeutic implications.

Cytopathologic diagnosis of bronchioloalveolar carcinoma: does it correlate with the 1999 World Health Organization definition?Am J Clin Pathol. 2004 Jul;122(1):44-50.

We identified 29 bronchial washing, bronchoalveolar lavage, sputum, and fine-needle aspiration specimens with corresponding surgical pathology specimens with features of bronchioloalveolar carcinoma (BAC). Surgical pathology correlates were reclassified according to the 1999 World Health Organization classification into pure BAC, mixed adenocarcinoma-BAC (AD-BAC), and papillary adenocarcinoma (PAP-AD). Twelve cases of invasive pulmonary adenocarcinoma (INV-AD) without a bronchioloalveolar component were reviewed for comparison. The cytology slides were evaluated for 12 features of BAC. No statistically significant feature permitted separation of BAC from AD-BAC or from PAP-AD. However, comparison of BAC with INV-AD identified 9 statistically significant cytologic features: clean background, absence of 3-dimensional clusters, neoplastic cells in flat sheets, orderly arrangement of cells with round uniform nuclei, predominance of mucinous cells, absence of nuclear overlap, absence of irregular nuclear membranes, fine granular chromatin, and nuclear grooves that were features of BAC cases. Although cytologic evaluation cannot prospectively diagnose BAC, the bronchioloalveolar pattern may be recognized and suggests in situ proliferation that is present in BAC, AD-BAC, or PAP-AD. The bronchioloalveolar pattern must be correlated with clinical, radiographic, and histologic parameters to determine whether the tumor is localized, multifocal, or diffuse and whether there is parenchymal invasion.

Bronchioloalveolar carcinoma: diagnostic pitfalls and immuno- cytochemical contribution.Diagn Cytopathol. 1998 Apr;18(4):301-6.

Because bronchioloalveolar carcinoma (BAC) commonly displays bland cytologic appearance, there is a good potential for misinterpretation. The aim of this study was twofold: one was to identify the most reproducible cytomorphologic features to distinguish BAC from conventional lung adenocarcinoma (CLA) on fine-needle aspiration (FNA), and the other was to investigate the staining characteristics of these two variants of lung carcinoma with P53 tumor suppressor gene immunostain and their potential value in the distinction between the two entities. Cytology records of 13 histologically documented BACs was retrieved: 7 FNA, 3 bronchial washing/bronchial brushing (BW/ BB), and 3 scraping smears of surgical specimens. Two cases had both FNA and BW/BB material. Immunostains for P53 protein, carcinoembryonic antigen (CEA), and Ki67(MIB-1) monoclonal antibodies were performed on 13 BACs (FNA cell blocks and tissue) and on 11 FNA cell blocks of CLA. Cytologically, BAC showed uniform cells with abundant, lacy cytoplasm, and bland, folded nuclei arranged singly, in papillary clusters, and sheets. Immunocytochemically, one BAC and one CLA were technically unacceptable. Of the 12 remaining BAC cases, 10 were reactive with CEA, 9 reactive with Ki67 (> 5%), and 4 reactive with P53. Of the 10 remaining CLAs, 9 were positive with CEA, 9 were reactive with Ki67 (> 5%), and 8 were reactive with P53. We conclude that BAC demonstrates distinctive cytologic features, but difficulty may be encountered with well-differentiated CLA, metastatic adenocarcinoma, and other lesions. Immunocytochemically, CEA and Ki67 do not appear to be discriminate, but P53 may be of value in distinguishing BAC from CLA. Attention to subtle nuclear changes, characteristic grouping, cellular arrangement, and P53 reactivity could enable cytopathologists to accurately diagnose BAC.

Cytology and immunocytochemistry of bronchioloalveolar carcinoma.Acta Cytol. 1987 Nov-Dec;31(6):717-25

A study of the value of cytologic examination in the diagnosis of bronchioloalveolar carcinoma showed that fine needle aspiration (FNA) cytology is a definitive means of making the diagnosis of bronchioloalveolar carcinoma. In experienced hands, FNA cytology approached a diagnostic accuracy of 100%. With exfoliative cytology, technically adequate sputum samples offered an 82% diagnostic yield; sputum cytology should thus be considered as an adjunct method in establishing the diagnosis. Several cytologic features that strongly suggest the diagnosis of bronchioloalveolar carcinoma and help to differentiate it from adenocarcinomas of other body sites are outlined. It is also concluded that immunocytochemical stains have limited value in differentiating bronchioloalveolar carcinoma and other types of clear cell malignant neoplasms, including mesothelioma, unless a panel of antibodies is used, and are of no value in ascertaining whether the cells are benign or malignant.

Value of sputum cytology in the differential diagnosis of alveolar cell carcinoma from bronchogenic adenocarcinoma.Acta Cytol. 1981 May-Jun;25(3):255-8.

A total of 90 cases in which a cytologic diagnosis of pulmonary adenocarcinoma has been previously made by consecutive sputum cytology were reviewed in order to estimate the possibility of a correct differential diagnosis of alveolar cell carcinoma (bronchioloalveolar) from bronchogenic adenocarcinoma. The diagnosis by sputum cytology in all cases was correlated with data from a subsequent biopsy, operation or autopsy. Using certain specific differential diagnostic cytologic parameters, striking differences were noted in the exfoliated cells in sputum samples; these related to cell size, clustering effects, pleomorphism, mucin production, cytoplasm, nuclei and nucleoli. Based on the observations made in this study, it is suggested that sputum cytology is not only a valuable method of detecting malignant cells but can also be quite useful to correctly type all cases of alveolar cell carcinoma and 93.75% cases of bronchogenic adenocarcinoma.

Bronchiolo-alveolar carcinoma: a correlative clinical and cytologic study.Cancer. 1978 Dec;42(6):2759-67

From 1970 to 1977, 101 patients with bronchiolo-alveolar carcinoma were admitted to the Toronto General Hospital. Cytology preparations from 97 patients were reviewed and analyzed in correlation with biologic behavior of the tumours. The value of cytologic diagnosis was reassessed. It appears that routine cytology methods were of limited value in the investigation of patients with a peripheral solitary tumor and therefore, percutaneous fine needle aspiration with positive results in 92% of cases examined, was the only useful cytologic examination for this type of lesion. For multicentric tumors, routine cytology methods achieved positive results in 87.9% of cases and fine needle aspiration 100%. Based on cytomorphologic features, bronchioloalveolar carcinoma can be subclassified into three types: secretory, nonsecretory and poorly differentiated. In this series, 84% of solitary tumors were secretory or nonsecretory type with favorable prognosis, and 16% of solitary tumors were poorly differentiated type with poor prognosis. 55.2% of multicentric tumors were poorly differentiated type and 77.3% of multicentric tumors showed positive lymph nodes at surgery. Our results demonstrate that patients with multicentric or poorly differentiated tumors had poor prognosis.

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