Epithelial Cell Atypia in Bronchoalveolar Lavage Specimens from Lung Transplant Recipients

Abstract

In lung transplant recipients, bronchoalveolar lavage (BAL) is mainly performed to detect infectious agents. However, in addition to microorganisms, epithelial cell atypia may be identified, and determination of its significance is necessary. Specimens obtained at BAL in lung and heart-lung transplant recipients (LTRs) between 1991 and 1998 were examined for the presence of significant cytologic atypia in epithelial cells. Ten cases in 9 patients were identified, and these composed the core of our study. These transplant BAL specimens were compared with 4 BAL specimens with carcinoma from non-transplant patients (NTPs). Fourteen cytologic parameters were evaluated, and clinical and biopsy correlation was made in each case. Significant overlap in cytologic features, including background cellularity, number of atypical cell clusters, number of cells in each cluster, size of cell clusters, contour of clusters, 3-dimensionality, tenacious intercytoplasmic connections, multinucleation, nuclear size, nuclear/cytoplasmic ratio, nuclear membrane irregularity, chromatin pattern, intranuclear inclusions, and nucleolar characteristics, was observed between atypical LTR cases and NTP carcinoma cases. Clinically, all LTR cases derived from nonneoplastic conditions including harvest injury (diffuse alveolar damage), acute cellular rejection, and infections. Our study results show that evaluation of cytologic features alone does not permit differentiation of atypical cells found in nonneoplastic conditions from those in malignant conditions. Clinical and histologic correlation and awareness of the range of atypia seen in posttransplant syndromes is important in correct interpretation of these cases.

Reactive Type II Pneumocytes in Bronchoalveolar Lavage Fluid

“…15 The morphologic appearance of RPII on MGG-stained slides varied, in line with previous descriptions. 4,5,16,17 This variation in morphology may reflect intermediate stages in the differentiation of RPII to type I epithelial cells 13 and may explain the different intensities of alkaline phosphatase staining in the present series. Further, the epithelial origin of the RPII cells was confirmed by reaction with monoclonal antibodies against cytokeratin 7 (a quitespecific phenotype of type II epithelial alveolar cells), and the cells were demonstrated to be in the proliferative phase (marked by Ki-67 monoclonal antibodies), as previously demonstrated on histologic preparations obtained from patients with diffuse alveolar damage.…”

“…5,17 Careful clinicopathologic evaluation is necessary to ensure an accurate diagnosis. 4,5,16 With regard to the present study, several factors apart from high prevalence argue for the nonneoplastic nature of the observed cells. None of the patients with RPII presented with localized mass lesions suspected of being primary or metastatic carcinoma, but instead they presented with a rapid clinical course and a clinical picture of acute pulmonary damage.…”

“…4,5,24,25 In particular, bronchoalveolar carcinoma must be ruled out. Subtle morphologic cytologic characteristics suggesting either RPII or carcinoma have been listed, 4,24,25 but these features have considerable overlap 16 and are better evaluated on Papanicolaoustained preparations than on MGG-stained ones. 26 Further, no single immunohistochemical marker accurately discriminates between both cell types; e.g., RPII may react with monoclonal antibodies against carcinoembryonic antigen and B72.3 (a marker for the tumor-associated TAG-72 antigen).…”

Diffuse Alveolar Damage

“…Both types of cell cluster were often associated with dense, basophilic, amorphous material (Figures 2A, 4A and Bronchoalveolar lavage (BAL) is a sensitive and safe diagnostic procedure that is widely used in the diagnosis of pulmonary disorders. [1][2][3][4][5][6][7][8] Although used predominantly for the detection of opportunistic infections in immunocompromised hosts, 9 BAL is also useful in the detection of lung cancer, 10 evaluation of interstitial lung disease, 11 diagnosis of drug-induced pulmonary toxicity 4 and monitoring of pulmonary acute allograft rejection. 12 BAL fluid has been extensively studied in diffuse alveolar damage (DAD) in the clinical context of adult respiratory distress syndrome (ARDS).…”

Cytologic Findings in Allogeneic and Autologous Bone Marrow Transplant Patients with Pulmonary Symptoms

“…6 It is well known that marked cellular atypia may be seen in respiratory cytology specimens secondary to infections, acute respiratory distress syndrome, chronic lung disorders, acquired immunodeficiency syndrome and cytoreductive treatments. 1,[6][7][8][9] In acute respiratory distress syndrome (ARDS), BAL can recover a large number of hyperplastic type II pneumocytes that may form gland-like structures and 3-dimensional groups having cells with high N/C ratios, prominent nucleoli and irregular nuclear outlines mimicking adenocarcinoma. 1,[8][9][10] The timing of BAL in patients with ARDS is important because hyperplastic type II pneumocytes are not seen before 3 days after the acute onset of alveolar damage in histologic studies.…”