Community‐acquired lobar pneumonia caused by Pseudomonas aeruginosa infection in Japan: A case report with histological and immunohistochemical examination

Pseudomonas aeruginosa is a common pathogen in nosocomial and/or healthcare‐associated pneumonia, but is rare in community‐acquired pneumonia. A 50‐year‐old previously healthy woman was taken to the emergency department because of rapidly progressing dyspnea. Chest radiograph showed consolidation of the entire right upper lobe, a finding suggestive of lobar pneumonia. The patient died of respiratory failure with bronchial bleeding, on the same day of admission. Autopsy revealed that the alveoli throughout the upper right lobe were filled with dense inflammatory cells mainly consisting of macrophages and neutrophils. Immunoreactive bacilli by using an anti‐P. aeruginosa antibody were localized within macrophages accumulated in the alveoli as well in the vessel walls. Lobar pneumonia composed of dense neutrophils and bacteria‐laden macrophages with total lung congestion and edema may be characteristic for community‐acquired P. aeruginosa pneumonia in a healthy adult.     

Extrinsic allergic alveolitis as an uncommon diagnostic pitfall in lung cytology

House paints, the industrial products of toxic chemicals are known to be linked with severe respiratory disturbances especially in inadequately ventilated places. In this study, we aimed to report a biopsy-proven case of extrinsic allergic alveolitis (EAA) who presented with nonspecific respiratory symptoms 1 month after having her whole house interior painted. At CT scanning, we observed the ground glass opacities and the micronodular pattern typical for EAA and also a solid, consolidative lung area, highly suggestive of malignancy. The case initially was misinterpreted as a malignant tumor both radiologically and cytologically at CT-guided transthoracic fine needle aspiration biopsy. The final pathologic diagnosis was given as EAA on frozen section performed during thoracotomy operation. The patient received short-term steroid treatment and has been doing well for the last 7 months after her operation. As a conclusion, when assessing a cytologic material from a patient who has got a solid lung mass and also a history of chemical dye exposure, consolidative mass formation which is a rare form of EAA should always be kept in mind. Another final point is that the appropriate ventilation should be achieved if the exposure with the house paint chemicals is inevitable.     

Platelet-activating factor increases pulmonary microvascular permeability and induces pulmonary edema. A preliminary report

Platelet-activating factor, a naturally occurring lipid that is released from leukocytes and alveolar macrophages, increased the flow of protein-rich lymph from the lungs and induced pulmonary edema in dogs when given in picomolar doses. The pulmonary edema was due to increased microvascular permeability, probably secondary to endothelial cell injury. These observations suggest that platelet-activating factor may be a mediator of high-permeability pulmonary edema in the "respiratory distress syndrome" complicating acute lung injury.     

Pulmonary crystal‐storing histiocytosis diagnosed by computed tomography‐guided fine‐needle aspiration

Crystal‐storing histiocytosis (CSH) is a rare process most often occurring in conjunction with an underlying hematopoietic neoplasm, usually multiple myeloma or low‐grade B‐cell lymphoma. We report the first case of pulmonary CSH diagnosed by fine‐needle aspiration biopsy. A patient with a history of urothelial carcinoma developed a lung nodule, which was evaluated by fine‐needle aspiration biopsy. Cytologic examination revealed macrophages with abundant cytoplasmic crystals diagnostic of CSH. Based on this cytologic interpretation, additional clinical laboratory evaluation was pursued and revealed a previously unknown monoclonal serum protein. CSH must be differentiated from other non‐neoplastic and neoplastic lesions and when diagnosed, should trigger a search for an underlying lymphoproliferative disorder. Diagn. Cytopathol. 2010. © 2009 Wiley‐Liss, Inc.     

Comparison of cytologic features of giant-cell tumor and giant-cell tumor of tendon sheath

The cytologic features in twelve cases of giant-cell tumor (GCT) and five cases of giant-cell tumor of tendon sheath (GCTTS) diagnosed by fine-needle aspiration cytology (FNAC) are described. All of these cases were histopathologically confirmed. The aspirates of GCT are composed of a dual population of mononucleated spindle cell and multinucleated giant cells. The peripheral adherence of giant cells to the spindle cell is the feature of diagnostic significance in GCT. In GCTTS, the aspirate consists of a polymorphic population composed of mononuclear histiocyte-like cells, hemosiderin laden macrophages, foamy macrophages, and a few multinucleated giant cells. FNAC can be used as a diagnostic tool for an early and accurate detection of these two giant cell-rich lesions, since the cytologic features when evaluated in conjunction with the clinical and radiologic features are sufficiently diagnostic.     

Pneumocytoma (sclerosing hemangioma), a potential pitfall

Pneumocytoma is an uncommon benign tumor of the lung, derived from primitive respiratory epithelium, with a predilection for middle‐aged females. A single, well‐circumscribed mass is commonly identified on imaging, necessitating pathologic evaluation for further assessment. Fine‐needle aspiration cytology is a minimally invasive and cost‐effective method that can be utilized in the diagnosis of these lesions. Yet, distinction of pneumocytoma from other entities such as well‐differentiated adenocarcinoma or carcinoid tumor can be quite challenging. Herein, we describe a case initially misdiagnosed as lung adenocarcinoma on FNA that was proven to be pneumocytoma on subsequent resection. This report highlights the importance of recognizing key cytologic features of pneumocytoma, namely the papillary architecture, dual cell population, and the hemorrhagic background with foamy macrophages, among others. An accurate preoperative diagnosis of this entity provides optimal patient management, as conservative surgical excision is curative. Diagn. Cytopathol. 2017;45:744–749. © 2017 Wiley Periodicals, Inc.     

Adult wilms' tumor metastatic to the lung: Endobronchial ultrasound‐guided fine needle aspiration biopsy

Adult Wilms' tumor (WT) is a rare entity with less than 300 cases reported to date in the medical literature. Histologic and cytologic features of adult WT of the kidney are similar to findings in pediatric WT. While the lungs are noted to be the most frequent site of metastatic disease in the pediatric population, the incidence of lung metastases remains unknown for adult WT. A search revealed 38 cases of adult WT with lung metastases published to date in the English literature. Amongst these cases only two have utilized cytology of the lung lesions as a means to arrive at a final diagnosis. We report a case of adult WT metastatic to the lung that was initially diagnosed using endobronchial ultrasound‐guided fine needle aspiration biopsy. The aim is to compare the current cytologic and immunohistochemical findings with those cases previously published, to outline the cytologic features of adult WT metastatic to the lung, and to emphasize the significance of cytologic diagnosis in the work‐up of adult WT. Diagn. Cytopathol. 2014;42:950–955. © 2013 Wiley Periodicals, Inc.     

Hypoxia aggravates lipopolysaccharide-induced lung injury

The animal model of inflammatory response induced by intratracheal application of lipopolysaccharide includes many typical features of acute lung injury or the acute respiratory distress syndrome. A number of experimental investigations have been performed to characterize the nature of this injury more effectively. In inflammatory conditions, hypoxia occurs frequently before and in parallel with pulmonary and non-pulmonary pathological events. This current study was designed to examine the in vivo effect of hypoxia as a potentially aggravating condition in endotoxin-induced lung injury. Lipopolysaccharide, 150 microg, was instilled intratracheally into rat lungs, and thereafter animals were exposed to either normoxia or hypoxia (10% oxygen). Lungs were collected 2, 4, 6 and 8 h later. Inflammatory response and tissue damage were evaluated by quantitative analysis of inflammatory cells and mediators, surfactant protein and vascular permeability. A significantly enhanced neutrophil recruitment was seen in lipopolysaccharide-animals exposed to hypoxia compared to lipopolysaccharide-animals under normoxia. This increased neutrophil accumulation was triggered by inflammatory mediators such as tumour necrosis factor-alpha and macrophage inflammatory protein-1beta, secreted by alveolar macrophages. Determination of vascular permeability and surfactant protein-B showed enhanced concentrations in lipopolysaccharide-lungs exposed to hypoxia, which was absent in animals previously alveolar macrophage-depleted. This study demonstrates that hypoxia aggravates lipopolysaccharide injury and therefore represents a second hit injury. The additional hypoxia-induced inflammatory reaction seems to be predominantly localized in the respiratory compartment, underlining the compartmentalized nature of the inflammatory response.     

Cytologic and histologic findings of iron pill‐induced injury of the lower respiratory tract

In the airways, iron pill‐induced mucosal injury is uncommon and can lead to necrosis and stricture of the respiratory tracts. The process is characterized by mucosal ulceration with deposition of crystalline iron particles, and the diagnosis is usually made on tissue biopsies. We report a case of iron‐sulfate‐induced mucosal injury in the bronchial washing and biopsy of a patient receiving therapeutic oral iron supplementation with no known aspiration event. Clinically, the patient presented with hemoptysis, and bronchoscopy detected ulcerated main stem bronchus mucosa clinically suspicious for a neoplastic process. Bronchial washings revealed reactive epithelial cells and numerous histiocytes with both intracellular and extracellular refractile brown crystalline material, which was positive on iron stain. The histologic findings on biopsy showed mucosal ulceration with deposits of extracellular crystalline iron particles. These histologic changes are similar to those seen in iron pill‐induced mucosal injury of the upper gastrointestinal tract in patients with “iron pill” gastritis. The cytologic and histologic features of iron pill‐induced airway injury clinically can mimic cancer. The presence of extracellular and intracellular crystalline iron in the airway lumen and/or mucosa with associated varying degrees of ulceration and inflammation confirms the diagnosis. Diagn. Cytopathol. 2013;41:901–903. © 2012 Wiley Periodicals, Inc.     

Clofazimine crystals in alveolar macrophages from a patient with the acquired immunodeficiency syndrome.

An induced sputum specimen from a 35-year-old patient with the acquired immunodeficiency syndrome (AIDS) contained numerous bright orange-red needle-shaped crystal inclusions in his alveolar macrophages. Careful questioning revealed that he recently had been treated for 7 months with clofazimine (200 mg/d) for persistent Mycobacterium avium complex bacteremia. The striking cytologic finding observed is diagnosed easily if the characteristic morphologic appearance of the crystals and their location within the cytoplasm of macrophages and cells of the reticuloendothelial system is appreciated. Although this is the first observation at San Francisco (Calif) General Hospital of clofazimine crystals in a respiratory specimen from a patient with AIDS, the potential of more widespread therapy with clofazimine in patients with AIDS who are infected with M avium complex makes it imperative that the microscopic appearance of these crystals be recognized.     

The “drunken honeycomb” feature of pulmonary mucinous adenocarcinoma: A diagnostic pitfall of bronchial brushing cytology

Pulmonary mucinous adenocarcinoma (PMA) is the terminology recently proposed in the new International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society (IASLC/ATS/ERS) International Multidisciplinary Classification of Lung Adenocarcinoma Guidelines for most tumors previously classified as mucinous bronchioloalveolar carcinomas (mBACs). PMA is histologically characterized by lepidic growth and at least some degree of invasive growth of goblet or columnar neoplastic cells with abundant intracytoplasmic mucin. We report here the cytologic features of PMA in a bronchial brushing specimen. The patient is an 84‐year‐old woman with a persistent dense consolidation in the right middle lobe of the lung found on non‐contrast computed tomography (CT) scan. Bronchial brushing smears showed a monotonous population of columnar neoplastic cells forming “drunken honeycomb”‐like cell clusters. The neoplastic cells displayed inconspicuous cytologic atypia. The concurrent transbronchial tissue biopsy and the resection specimen confirmed the diagnosis of PMA. Due to the bland nuclear features, the neoplastic cells in the bronchial brushing specimen were interpreted as benign at the time of the initial diagnosis, demonstrating a diagnostic pitfall of bronchial brushing cytology. A high index of suspicion is recommended when a lung lesion with “drunken honeycomb”‐like cell clusters is encountered in bronchial brushing specimens. The review of the literature regarding the recently designated PMA is presented. Diagn. Cytopathol. 2013. © 2011 Wiley Periodicals, Inc.     

Neonatal lung immune responses show a shift of cytokines and transcription factors toward Th2 and a deficit in conventional and plasmacytoid dendritic cells

The high incidence of lung‐damaging life‐threatening respiratory infections in infants may be related to the immaturity of their immune systems. To determine whether lung immune features differ in early life compared with those in adulthood, whole lung as well as lung T lymphocyte and DC responses were investigated in BALB/c neonates versus adults. Higher expression of GATA‐3 and rapid and sustained production of type 2 cytokines by lung explants after in vitro exposure to anti‐CD3 was the hallmark of the neonatal period, suggestive of a Th2 bias. Neonatal lung GATA‐3‐producing cells were identified as CD3⁺, CD4 and CD8 double‐negative T lymphocytes, a subset found at a higher frequency in neonatal than adult lung. The neonatal lungs contained fewer conventional DCs, with a lower ratio of CD103⁺ to CD11b⁺ DCs, and a much lower number of plasmacytoid DCs in comparison with adult lungs. Yet, when stimulated in vivo by BCG, neonatal lung DCs matured and primed adult naïve CD4⁺ T cells toward Th1 as efficiently as adult BCG‐primed lung DCs. Conversely, both adult and neonatal BCG‐primed lung DCs induced a Th2 cytokine response from neonatal naïve lymph node T cells, suggestive of an intrinsic feature of neonatal T lymphocytes.     

肺巨噬细胞在肺损伤修复和再生中的作用

肺脏作为与外界直接相通的器官,容易在病原微生物以及其它理化因素的作用下发生组织损伤。既往研究认为,肺脏是一个高度沉默的器官,其再生能力有限。但是,新近的一些研究发现,肺内存在多种上皮祖细胞或干细胞群, 在肺损伤发生过程中这些细胞可被激活、分化,进而促进肺组织的再生。肺内存在多种亚型巨噬细胞,其在肺损伤的不同阶段均发挥着重要的作用,且与损伤后肺组织的再生密切相关。通过精细的干预单核/巨噬细胞的分化可能是减轻肺损伤、 促进肺再生的有效手段。     

Merkel cell carcinoma presenting as a malignant pleural effusion post-COVID-19 hospitalization: A case report and literature review

Merkel cell carcinoma (MCC) is a rare, highly aggressive neuroendocrine carcinoma of the skin, associated with immunosuppression, UV light exposure, and the Merkel cell polyomavirus (MCPyV). Cases of metastatic MCC diagnosed in body fluid cytology are extremely rare; only five cases have been reported previously in the English literature. We present a case of a 65-year-old male with acute respiratory failure and an enlarged right pleural effusion. He had two hospitalizations for COVID-19 pneumonia 2 months prior, for which he received steroid treatment and tocilizumab. Emergent thoracentesis was done, with pleural fluid sent for cytologic evaluation. Both the Papanicolaou stained ThinPrep slide and cell block demonstrated clusters of predominantly small to medium sized blue round cells with hyperchromatic nuclei, scant cytoplasm and fine chromatin, in a background of rare mesothelial cells, macrophages and numerous lymphocytes. Tumor cells were positive for CD56, chromogranin, synaptophysin, SAT2B, MCPyV, and CK20 in perinuclear dot like pattern, while negative for TTF-1 and CD45 immunostains. Ki67 proliferative index was approximately 40%. The patient had a history of MCC of the right ulnar forearm 4 years before the current presentation, which was unknown to us at the time of cytologic evaluation. To the best of our knowledge, this is the sixth case of metastatic MCC diagnosed by fluid cytology and the first reported in a patient receiving immunosuppressive treatment for COVID-19. Further reporting of such cases may increase awareness, especially when prior history is not readily available, such as in our case.     

The volatile anaesthetic sevoflurane attenuates lipopolysaccharide‐induced injury in alveolar macrophages

Acute lung injury (ALI) is a well‐defined inflammation whereby alveolar macrophages play a crucial role as effector cells. As shown previously in numerous experimental approaches, volatile anaesthetics might reduce the degree of injury in pre‐ or post‐conditioning set‐ups. Therefore, we were interested to evaluate the effect of the application of the volatile anaesthetic sevoflurane on alveolar macrophages regarding the expression of inflammatory mediators upon lipopolysaccharide (LPS) stimulation in vitro. Alveolar macrophages were stimulated with LPS. Two hours later, cells were exposed additionally to air (control) or to sevoflurane‐containing air for 4, 6, 8, 12 or 24 h. Tumour necrosis factor (TNF)‐α, cytokine‐induced neutrophil chemoattractant‐1 (CINC‐1), macrophage‐inflammatory protein‐2 (MIP‐2) and monocyte chemoattractant protein‐1 (MCP‐1) proteins were determined and chemotaxis assays were performed. To evaluate possible cellular signalling pathways phosphorylation of the kinases extracellular‐regulated kinase (ERK) and Akt was assessed. In the early phase of sevoflurane post‐conditioning expression of TNF‐α, CINC‐1, MIP‐2 and MCP‐1 was attenuated, leading to a diminished chemotaxis reaction for neutrophils. Phosphorylation of ERK seems to be a possible cellular mechanism in the sevoflurane‐induced protection in vitro. Pharmacological post‐conditioning of alveolar macrophages with sevoflurane immunmodulates the inflammatory response upon stimulation with endotoxin. This might be a possible option for a therapeutical approach in ALI.     

The role of cyclooxygenase-2 in mechanical ventilation-induced lung injury

Mechanical ventilation is necessary for patients with acute respiratory failure, but can cause or propagate lung injury. We previously identified cyclooxygenase-2 as a candidate gene in mechanical ventilation-induced lung injury. Our objective was to determine the role of cyclooxygenase-2 in mechanical ventilation-induced lung injury and the effects of cyclooxygenase-2 inhibition on lung inflammation and barrier disruption. Mice were mechanically ventilated at low and high tidal volumes, in the presence or absence of pharmacologic cyclooxygenase-2-specific inhibition with 3-(4-methylsulphonylphenyl)-4-phenyl-5-trifluoromethylisoxazole (CAY10404). Lung injury was assessed using markers of alveolar-capillary leakage and lung inflammation. Cyclooxygenase-2 expression and activity were measured by Western blotting, real-time PCR, and lung/plasma prostanoid analysis, and tissue sections were analyzed for cyclooxygenase-2 staining by immunohistochemistry. High tidal volume ventilation induced lung injury, significantly increasing both lung leakage and lung inflammation relative to control and low tidal volume ventilation. High tidal volume mechanical ventilation significantly induced cyclooxygenase-2 expression and activity, both in the lungs and systemically, compared with control mice and low tidal volume mice. The immunohistochemical analysis of lung sections localized cyclooxygenase-2 expression to monocytes and macrophages in the alveoli. The pharmacologic inhibition of cyclooxygenase-2 with CAY10404 significantly decreased cyclooxygenase activity and attenuated lung injury in mice ventilated at high tidal volume, attenuating barrier disruption, tissue inflammation, and inflammatory cell signaling. This study demonstrates the induction of cyclooxygenase-2 by mechanical ventilation, and suggests that the therapeutic inhibition of cyclooxygenase-2 may attenuate ventilator-induced acute lung injury.     

Lung metastases of a uterine tumor resembling ovarian sex‐cord tumor: Report of a rare case

Uterine tumor resembling an ovarian sex‐cord tumor (UTROSCT) is a rare type of uterine neoplasm. We present an extremely rare case of lung metastases from a UTROSCT focusing on the cytologic features. A 69‐year‐old Japanese woman was admitted to our hospital for further examination and treatment for abnormal shadows in the right lung field. She had a history of total hysterectomy for UTROSCT. Moreover, she underwent wedge resection of the right middle lobe for lung metastasis of UTROSCT in 2011. Enhanced chest computed tomography scan revealed a solid nodule 8 mm in diameter in the right upper lobe and a well‐demarcated 33‐mm mass or nodule in the lower lobe. Under the diagnosis of metastatic tumors from UTROSCT, she underwent wedge resection of the right upper lobe and segmentectomy of the right S8. Cytologically, the stump smear from the resected tumors revealed round to short spindle‐shaped neoplastic small cells arranged in sheets with poor cohesion and no cluster formation. The nuclei were irregular in shape, and the chromatin was finely granular, uniform, and increased. Mitotic figures were not observed. Necrosis was absent in the background. Histologically, the final diagnosis was UTROSCT group II. This is an unusual case of metastatic UTROSCT to the lung in which the cytologic features are described.     

Role for macrophage migration inhibitory factor in acute respiratory distress syndrome

The critical role of macrophage migration inhibitory factor (MIF) in mediating inflammatory lung injury in acute respiratory distress syndrome (ARDS) has been raised recently. The present study has identified enhanced MIF protein expression in alveolar capillary endothelium and infiltrating macrophages in lung tissues from ARDS patients. The possibility that MIF up-regulates its synthesis in an autocrine fashion in ARDS was tested using cultured endothelial cells stimulated with MIF and a murine model of lipopolysaccharide (LPS)-induced acute lung injury. MIF induced significant MIF and tumour necrosis factor (TNF)-alpha synthesis in cultured endothelial cells and the effect was blocked by neutralizing anti-MIF antibody. A similar blocking effect was observed when MIF-stimulated endothelial cells were pretreated with neutralizing anti-TNF-alpha antibody or glucocorticoid, supporting the notion that MIF induced TNF-alpha production via an amplifying pro-inflammatory loop. Treatment with anti-MIF or glucocorticoid effectively attenuated pulmonary pathology and the synthesis of MIF or TNF-alpha in mice with LPS-induced acute lung injury. Mildly augmented expression of aquaporin 1 (AQP1) was also detected in alveolar capillary endothelium in ARDS. In vitro studies revealed that both MIF and TNF-alpha induced a small increase of AQP1 synthesis in cultured endothelial cells. These findings suggest that MIF plays a crucial pathological role leading to alveolar inflammation in ARDS. Anti-MIF and early glucocorticoid therapy may represent a novel therapeutic approach for reducing alveolar inflammation in ARDS.     

Cribriform‐morular variant of papillary thyroid carcinoma—Cytological and immunocytochemical findings of 18 cases

The purpose of this article was to describe cytologic findings of cribriform‐morular variant of papillary thyroid carcinoma (CMV‐PTC) in detail, to review previously reported cases, and to emphasize the diagnostic significance of this subtype. We examined 19 ultrasound‐guided fine needle aspiration (FNA) specimens from 18 CMV‐PTC patients. Cytologic features of CMV‐PTC were as follows, (1) hypercellularity, (2) papillary arrangement composed of tall columnar cells, (3) cribriform pattern, (4) morules, (5) spindle cells, (6) obscure ground‐glass nuclei, (7) peculiar nuclear clearing (PNC), (8) foamy or hemosiderin‐laden histiocytes, (9) hyaline materials, (10) absence of colloid in the background. The nuclear and cytoplasmic immunoreactivity of beta‐catenin and biotin‐positive PNC can indicate CMV‐PTC. We believe that cytologic diagnosis of CMV‐PTC is possible and it may lead to the early detection of polyposis coli. Diagn. Cytopathol. 2010;38:890–896. © 2010 Wiley‐Liss, Inc.     

Pulmonary alveolar proteinosis: a spectrum of cytologic, histochemical, and ultrastructural findings in bronchoalveolar lavage fluid

Pulmonary alveolar proteinosis (PAP) is defined as abundant extracellular proteinaceous periodic acid-Schiff (PAS)-positive material which represents surfactant distending alveolar spaces. While this lesion is defined by histologic findings, there are characteristic radiologic features and cytologic findings in bronchoalveolar lavage (BAL) specimens that together may provide a confident diagnosis. The BAL specimens from all patients for which a diagnosis of PAP was made or suggested on either cytologic or biopsy specimens at University of North Carolina Hospitals from 1990-1999 were reviewed. There were 23 cytologic specimens from 11 patients. Patient ages ranged from 6 wk to 76 yr. All 23 specimens had slides prepared for Papanicolaou stain, 22 specimens (all patients) had Diff-Quik stains, 10 specimens (6 patients) had PAS stains, and 8 specimens (5 patients) had lipid stains. Nine patients had lung biopsies in addition to cytologic specimens. The clinical charts of all patients were reviewed. Twenty-one cytologic specimens were described as cloudy or milky, and 2 were bloody. By chart review and/or biopsy results, 8 patients were felt to have definite PAP. The initial lavage specimens from 6 of these patients showed classic cytologic findings of PAP, consisting of paucicellular specimens dominated by adundant extracellular granular to globular material which was basophilic on Diff-Quik stain, pale to focally eosinophilic on Pap stain, and PAS-positive, diastase-resistant. Five of these patients had biopsies; 3 showed PAP, and 2 were insufficient. Later BAL specimens after therapeutic lavage from these patients were often less characteristic, with scant extracellular material present. The other 2 patients with PAP clinically and by biopsy had atypical cytologic findings, with one showing numerous macrophages with scant PAS-positive material and abundant lipid mimicking lipid pneumonia, and one showing moderate eosinophils in addition to the extracellular proteinacous material. The remaining 3 patients were felt not to have PAP clinically or by biopsy (1 lymphocytic interstitial pneumonitis, 1 rheumatoid lung, and 1 hemosiderosis), and their BAL specimens predominantly contained macrophages with rare proteinaceous extracellular globules. Electron microscopy was performed in 5 patients (4 considered to have PAP, and 1 with lymphocytic interstitial pneumonitis) and in all cases showed whorled myelin figures characteristic of surfactant. The PAP cases and the non-PAP case had identical ultrastructural findings. We conclude that BAL specimens with classic cytologic features and supporting clinical and radiographic evidence may be diagnosed as PAP. Atypical specimens should be approached with caution, and may represent either PAP or other pulmonary diseases with secondary accumulation of surfactant. Cytology specimens taken subsequent to therapeutic lavage from PAP patients may also not be diagnostic.