Australian Society of Cytology

CEC Resources

Respiratory Infections

Mark Stevens CFIAC
Principal Medical Scientist
Institute of Medical and Veterinary Science
Adelaide, Australia 5000

Copyright © All rights reserved. No part of this publication may be reproduced in any form or by any means without the permission of the author or Medvet Science Pty Ltd, the commercial agent for the Institute of Medical and Veterinary Science providing advice regarding protection of intellectual property
(e-mail address: intprop@medvet.com.au).

Cytology has an important role to play in the diagnosis of infectious disease, especially in the immuno-compromised host population. However, a diagnosis must be made in conjunction with knowledge of the patients clinical history and the results of microbiological and virological investigations. This section details those criteria which are helpful in the diagnosis of the more commonly encountered infections.

Viral

Cellular changes attributed to infection with herpes simplex virus are similar to those encountered in gynaecological specimens. The cells exhibit cytomegaly and multinucleation with margination of chromatin along the nuclear membrane. Nuclear moulding is also a feature and the nuclei have a ground-glass appearance. In respiratory specimens, especially sputa and bronchial washes, infected cells appear smaller and demonstrate fewer nuclei than their cervical smear counterparts. A single medium sized nuclear inclusion is usually identified surrounded by a perinuclear inclusion halo. No cytoplasmic inclusions are seen.

In contrast, cells infected with cytomegalovirus are larger and usually contain a single nucleus, again demonstrating margination of chromatin.

A single large nuclear inclusion body is usually identified giving the cell an "owls-eye" appearance. Small multiple cytoplasmic inclusion bodies are also present. These bodies are surrounded by peri-inclusion halos giving the cytoplasm a "buck-shot" appearance (Rosenthal, 1988).

Adenovirus is characterised by cytomegaly and occasional multinucleation (Rosenthal, 1988). Single or multiple nuclear inclusions are present.

These inclusions can be large enough to almost completely replace the nucleus. The cell retains its columnar shape; cilia and a well defined terminal bar can also be identified.

Accompanying the above changes is regenerative or reactive atypia of the bronchial epithelium which may cause problems in diagnosis.

A common finding in viral infection, especially adenovirus, is the degenerative change termed ciliocytophthoria (Johnston, 1991).

This change results in separation of the columnar cell into two parts: a part containing the degenerate nucleus surrounded by cytoplasm and a portion with the remaining cytoplasm and cilia attached.

Bacterial

A diagnosis of Mycobacterium tuberculosis can be suggested if acid fast bacilli, and accompanying granulomatous changes, are identified. The organism is more likely seen in sputum, BAL and FNA specimens (Johnston, 1991). The carbol fuchsin acid-fast stain by Ziehl and Neelson is used by most laboratories and the stain has a 99.98% positive detection rate on histological section (Murray, 1980; Auerbach, 1988). Low numbers of organisms are best identified by using auramine-o stains under fluorescence microscopy. "Negative images" of bacilli have been recently described in the cytoplasm of BAL histiocytes stained with giemsa (Maygarden, 1989). A pitfall in diagnosis is in patients treated with the drug clofazimine as these crystals can resemble the negative images of mycobacterial infection (Silverman, 1993). The cellular pattern, although not specific for tuberculosis, can be helpful. Features identified include multinucleated histiocytes, epithelioid cells, microcalcifications, lymphocytes and necrotic debris.

Actinomyces israelii is a normal inhabitant of the tonsillar region and demonstration of tissue invasion is required for a diagnosis of actinomycosis.

In cytological material the organisms are usually present in clusters surrounded by hyalinised eosinophilic material (Splendore-Hoeppli reaction)(Chandler, 1988). Gram staining of these "sulphur granules" reveal gram positive branching filaments approximately 1 m in diameter. The organisms can be identified with papanicolaou (PAP) and haematoxylin and eosin (H & E) stains and filament granules can be demonstrated with the periodic acid schiff (PAS) stain. The filaments also stain with the methenamine silver procedure (GMS).

Nocardia asteroides is the organism most commonly involved in Nocardiosis in humans. The organism appears as delicate, branched, beaded filaments which can be difficult to discern on H & E and PAP stained preparations. With these stains the organism cannot be differentiated from other filamentous bacteria such as Streptomyces. Darkly stained fibrin fibres can also mimic the organism and examination of gram stained smears under oil immersion is usually required. The GMS stain is preferred and highly branched organisms stained with GMS have been described as resembling "chinese characters". Included in the differential diagnosis is mycobacterium tuberculosis, however the organism does not stain well with the standard Ziehl-Neelson procedure despite being referred to as an acid-fast organism (Blackmon, 1988). It is difficult to detect the organism in sputum and nocardia has been rarely diagnosed by FNA (Busmanis, 1995).

Bacteria of the genus Legionella are the causative agents of Legionnaires disease. The organism is difficult to demonstrate on smears or histological section. They stain poorly with gram and inconsistently with giemsa. Silver impregnation stains, such as Warthin-Starry and the Dieterle procedure, are recommended (Chandler, 1977). The organisms appear as small bacilli up to 1 m wide and 2 - 4 m in length. Improved sensitivity in detection can be achieved with the use of immunofluorescence microscopy.

Fungi

Pulmonary histoplasmosis is commonly caused by the fungus Histoplasma capsulatum. The disease is characterised by the presence of uniform spherical-oval yeast-like cells in the cytoplasm of macrophages, although these can be difficult to discern with H & E and PAP due to their small size ( 2 - 4 m diameter). The organism is uninucleate and can have single buds. Pseudohyphae and germ tubes can be seen in more active lesions. With conventional stains the cytoplasm is retracted from the poorly stained cell wall creating an impression of a "halo". This "halo" suggests the presence of a capsule but special stains do not confirm this. The organism is best seen with GMS although the cell wall can also be demonstrated with PAS and cresyl violet stains (Bancroft, 1977). In specimens where multiple infectious organisms are found, intra- and extracellular localisation is important in diagnosis. This can be aided with the GMS stain using H & E as a counterstain (Blumenfeld, 1991). The GMS stain is also helpful in differentiating the organism from calcified debris in the background especially on histological section. A number of organisms can mimic H. capsulatum and need to be considered in the differential diagnosis. Capsule deficient forms of Cryptococcus neoformans can have similar appearances but usually some capsule remnants can be identified with the mucicarmine stain. Microforms of Blastomyces dermatitidis are usually multinucleated, with thick double contoured walls and broad based budding. The distinction between H. capsulatum and yeast forms of Torulopsis glabrata may be difficult and require immunofluorescent techniques (Kaplan, 1969). Leishmania and Toxoplasma can also resemble H. capsulatum but routine fungal stains are helpful in excluding these parasites. In GMS stains, cysts of Pneumocystis carnii may resemble H. capsulatum but the former are usually larger, have a central staining body and do not bud.

Cryptococcus neoformans presents as pleomorphic, uninucleate, thin walled yeast forms 2 - 20 m in diameter.

They are usually spherical to elliptical in shape and surrounded by a thick mucinous capsule. Single "tear-drop" budding is frequently seen and in active lesions chains of budding cells and short hyphae can be demonstrated (Chandler, 1988). C. neoformans can be identified with routine stains but special stains may be required if organisms are few in number. Cryptococcus is the only pathogenic fungus which produces capsular material and this can be demonstrated with mucicarmine, PAS or alcian blue. In sections stained with these techniques the capsule can have a spinous appearance due to shrinkage of the capsule during processing. Other stains which can be utilised include GMS (organism and its capsule are argyrophilic), toluidine blue O (wall and capsule are metachromatic) and alcian blue-PAS (body of fungus is stained red and the capsule is blue). On occasions the capsule and wall may be anisotropic under polarised microscopy (Bancroft, 1977). Poorly encapsulated forms of C. neoformans have been described in immunocompetent apparently healthy subjects (Harding, 1979). These organisms can be confused with H. capsulatum. However, some capsular material is usually identified and a modified Fontana-Masson stain is of assistance (Kwon-Chung, 1981). C. neoformans has been identified in a wide range of cytological specimens (Gupta, 1985; Rosen, 1982; Silverman, 1985).

Blastomycosis dermatitidis can be identified as intra- and extracellular spherical to oval multinucleated yeast-like cells approximately 8 - 15 m in diameter (Daniel, 1979; Johnston, 1970). The organism has thick refractile double-contoured walls and single broad-based buds. The bud has the tendency to remain in close proximity to the mother cell such that flattening of the two surfaces occurs. Occasionally, microforms in the size range of H. capsulatum can be seen but these are usually accompanied by a range of larger yeast forms. Germ tubes and hyphae are rarely formed in tissue. The organism can be identified in PAP and H & E stained preparations but special stains are usually required. These include PAS, GMS and cresyl violet which stain the cell wall. The fungi are metachromatic with the toluidine blue O stain (Bancroft, 1977). Improved detection is achieved with fluorescent antibody techniques (Kaplan, 1969). The fungi is distinguished from C. neoformans by broad based budding and lack of capsular material. Broad based budding is also helpful in differentiating this fungi from Coccidioides immitis, which contains numerous endospores, and H. capsulatum.

Coccidiodomycosis is caused by the dimorphic species Coccidioides immitis. The fungi presents as large (30 - 60 m) thick walled spherules.

These spherules are easily identified with conventional stains (Guglietti, 1968). The spherules contain numerous endospores 2 - 5 m in diameter. In section the spherules are surrounded by a radiating corona of eosinophilic Splendore-Hoeppli material. Hyphae and arthroconida are rarely seen except in lesions exposed to aerobic conditions. The wall and endospores of the fungus, as well as liberated endospores, are best identified by the GMS and PAS stains. Cresyl violet stains the cell wall pink (Bancroft, 1977). Crowded shrunken immature spherules can resemble B. dermatitidis and a careful search for well formed spherules is advised. Liberated endospores can be mistaken for H. capsulatum. However, the endospores of C. immitis are usually more pleomorphic and are generally associated with immature spherules or fragments of spherule walls. Haemosiderin laden macrophages can also be a problem in diagnosis (Guglietti, 1968) as are pollen granules and vegetable cells. Atypical reparative changes can be seen in association with the infection and misinterpretation of these changes as squamous cell carcinoma should be avoided (Chen, 1995).

Aspergillus fumigatus is the most common cause of pulmonary aspergillosis and is a frequent saprophyte in the lung.

The disease is often difficult to prove unless invasion of tissues can be demonstrated. The fungus can be seen with conventional stains but GMS is recommended. The fungus exhibits long uniform and septate hyphae 3 - 6 m in width. The hyphae have parallel contours and thick walls. Branches arise at acute (45) angles and the pattern of branching is described as progressive and dichotomous. Mycelium composing an aspergilloma can contain bizarre, swollen or globose hyphae up to 15 m in diameter (Chandler, 1988). Conidospores are usually found only on mucosal surfaces or in cavity lesions exposed to air but they have been reported in BAL fluid (Stanley, 1992). Fungal hyphae can be accompanied by eosinophils, charcot-leyden crystals and atypical metaplastic cells especially in allergic bronchopulmonary aspergillosis (Chen, 1993). Calcium oxalate crystals can also be seen in association with aspergillus. Aspergillus needs to be distinguished from other fungi that form branched, septate hyphae, for example fungi in the genera Fusarium and Pseudallescheria. Hyphae forms of candida can be separated due to the presence of yeast-like cells and pseudohyphae. Phycomycetes and exogenous fibres also need to be considered in the differential diagnosis. The hyphae of the containment alternaria can be distinguished from aspergillus by the presence of bulbous swelling at the ends of hyphae segments, near points of separation, and by the absence of 45 branching.

Candidiasis is caused by yeast-like fungi of the genus Candida. Laboratory diagnosis of the disease can be difficult as candida is part of the normal flora of the mouth and upper respiratory tract. Identification of candida in histological and cytological preparations is easy if both budding yeast-like cells, which are spheroidal-oval in shape and 2 - 6 m in diameter, and mycelial elements, including pseudohyphae and true hyphae, are present. The organism can be seen with conventional stains but the walls of the fungus are best demonstrated with GMS and PAS. The yeast-like cells may produce oval blastoconidia. Pseudohyphae are formed by elongation of budding yeast forms and the hyphae constrict at the point of attachment giving the hyphae segments an elliptical appearance. This is helpful in differentiating candida hyphae from those of aspergillus. True hyphae develop from spores rather than yeast cells. They are narrower (3 - 5 m) than pseudohyphae and do not exhibit constriction at points of septation. Candida can be separated from B. dermatitidis, C. neoformans, Torulopsis glabrata and H. capsulatum as the latter rarely produce pseudohyphae or hyphae in tissues. Aspergillus does not produce yeast forms. Artefacts can mimic candida and these include starch, vegetable cells and carbon pigment.

The term mucomycosis encompasses a variety of opportunistic fungi (Marchevsky, 1980; Chandler, 1988).

The term includes species within the genera Rhizopu, Absidia and Mucor amongst others. The fungi are characterised by broad (greater than 10 - 25 m width) pleomorphic hyphae which are thin walled, delicate and pauciseptate. The hyphae are often twisted, folded and wrinkled giving the impression that they are more septate than is the case. The pattern of branching is irregular and branches are often orientated at right angles. Hyphae are well demonstrated with stains such as GMS and PAS. The main infective agent to be included in the differential diagnosis is aspergillus, however this organisms has narrow and more uniform hyphae, are regularly septate and have an orderly, progressive dichotomous pattern of branching.

Parasites

Pneumocystis carinii can be diagnosed in a variety of cytological specimens of which BAL is the most sensitive (Orenstein, 1985; Fleury, 1985).

Identification of cyst forms and trophozoites establishes the diagnosis. Cup-shaped cysts of P. carinii are best demonstrated with GMS although toluidine blue O, PAS and Gram-Weigert stains all highlight the cyst wall. Cysts and trophozoites are not demonstrated with the H & E or the PAP stain. Detection of pneumocystis is enhanced using an indirect fluorescent antibody stain for the organism (Baughman, 1989). The cysts are approximately 6 - 8 m in diameter and are round, oval or cup-shaped. The cysts contain a dark staining single structure which represents thickening of the cell wall. This structure can appear as a dot, ring or comma. This feature is helpful in distinguishing P. carinii from yeasts, red blood cells and other cyst-like organisms.

Trophozoites can be identified with giemsa or toluidine blue stain.

Up to eight intracystic trophozoites can be identified often arranged in a circular pattern. Free nonencysted forms are more difficult to identify and may be confused with cell fragments and debris.

The intra-alveolar exudate associated with the organism is an important aid to diagnosis.

This exudate appears as a three dimensional cast with a honeycomb appearance. The casts have smooth borders and are usually packed with organisms. The presence of this exudate can be pronounced in massive infections such as those encountered in AIDS patients and may be considered diagnostic in these situations. However lack of casts is not sufficient to call a case negative for pneumocystis. Sampling error and a low organism load can result in false negative diagnoses and staining with GMS is advisable to confirm the diagnosis (Naryshkin, 1991; Dugan, 1988). Alveolar casts also have a different appearance in treated patients and can be a source of a false negative diagnosis (Naryshkin, 1991). Alveolar exudates stained with PAP exhibit apple-green fluorescence when exposed to ultraviolet light and this can aid detection (Ghali, 1984). Fungi of the genera Candida and Torulopsis may resemble P. carinii in size and shape. The demonstration of budding and absence of a central staining body can assist in diagnosis. Liberated endospores of C. immitis are approximately the same size as P. carinii. Although these endospores do not bud they fail to show a central staining body with GMS. H. capsulatum is usually smaller than P. carinii but features helpful in diagnosis include its intracellular localisation and budding. H. capsulatum can show a central staining body which creates problems in diagnosis (Watts, 1985). Red blood cells may also create diagnostic difficulties in preparations over stained with GMS.

The tachyzoites of Toxoplasma gondii can be identified in the cytoplasm of histiocytes with H & E and PAP. Examination of cells under oil immersion is advisable. The organisms are crescentric and slightly pyriform in shape and measure 4 - 8 m by 2 - 3 m (Baird, 1988). Identification of tachyzoites, cysts and pseudocysts is achieved with giemsa stains and morphology is best appreciated at the periphery of cytospin preparations of lavage fluid (Gordon, 1993). Differential diagnosis includes: H. capsulatum (stain with GMS and PAS, demonstrate budding), CMV (basophilic cytoplasmic inclusions can mimic T. gondii but presence of nuclear inclusions is suggestive of viral aetiology), Leishmania and Trypanosoma can exhibit intracellular forms but absence of a kinetoplast differentiates T. gondii from these parasites (Baird, 1988), precipitated stain artefact, necrotic debris and fibrin (Bottone, 1991).

The filariform larvae of Strongloides stercoralis can be identified in sputum. Infection is more often seen in patients with compromised immunity.

The larva measure 400 - 500 mm in length and has a characteristic notched tail. The organism also lacks a buccal cavity (Baird, 1988). The differential diagnosis includes Ascaris lumbricoides and hookworms, the latter can be distinguished from S. stercoralis by their sharply pointed tails. Free living rhabditiform larvae of other species, for example Rhabditis, can contaminate laboratory specimens and mimic S. stercoralis.

Echinococcosis is infection with larvae of Echinococcus granulosus.

Commonly called hydatid disease the larvae form cystic structures in intermediate hosts. The liver is the most common site of infection in adults (60 - 70%) with pulmonary involvement occurring in 20% of patients (Baird, 1988). Hydatid cysts in the lung can grow unnoticed and reach up to 20 cm in diameter. Pulmonary hydatid cysts are usually detected by cytology when cysts rupture and contents appear in sputum or when cysts are inadvertently sampled by fine needle aspiration. Diagnosis is confirmed by identifying the presence of hooklets, protoscolices or pieces of laminated cell wall (Garcia, 1986; Garret, 1977; Das, 1995).

REFERENCES

Auerbach O, Dail, DH. Mycobacterial Infections. In Pulmonary Pathology. Edited by DH Dail, SP Hammar. New York, Springer-Verlag, 1988.
Baird JK, et al. Parasitic Infections. In Pulmonary Pathology. Edited by DH Dail, SP Hammar. New York, Springer-Verlag, 1988.
Bancroft JD, Stevens A. Theory and Practice of Histological Techniques. Churchill Livingston, Edinburgh 1977.
Baughman RP, et al. The use of an indirect fluorescent antibody test for detecting pneumocystitis carinii. Arch Pathol Lab Med 1989;113:1062-1065.
Bedrossian CWM, Corey BJ. Abnormal sputum cytopathology during chemotherapy with bleomycin. Acta Cytol 1978;22:202-207.
Berman JJ, et al. Widespread post-tracheostomy atypia simulating squamous cell carcinoma. A case report. Acta Cytol 1991;35:937-947.
Bewtra C, et al. Exfoliative sputum cytology in pulmonary embolism. Acta Cytol 1983;27:489-496.
Blackmon JA. Bacterial Infections. In Pulmonary Pathology. Edited by DH Dail, SP Hammar. New York, Springer-Verlag 1988.
Blumenfeld W, Gan GL. Diagnosis of histoplasmosis in bronchoalveolar lavage fluid by intracytoplasmic localisation of silver positive yeasts. Acta Cytol 1991;35:710-712.
Bottone EJ. Diagnosis of acute pulmonary toxoplasmosis by visualisation of invasive and intracellular tachyozoites in giemsa stained smears of bronchoalveolar lavage fluid. J Clin Microbiol 1991;29:2626-2627.
Boucher LD, Yoneda K. Cytologic characterisation of bronchial epithelial changes in small cell carcinoma of the lung. Acta Cytol 1995;39:69-72.
Busmanis I, et al. Nocardiosis diagnosed by lung FNA: a case report. Diagn Cytopathol 1995;12:56-58.
Chandler FW, et al. Demonstration of the agent of legionnaires' disease in tissue. N Engl J Med 1977;297:1218-1220.
Chandler FW, Watts JC. Fungal Infections. In Pulmonary Pathology. Edited by DH Dail, SP Hammar. New York, Springer-Verlag 1988.
Chen KTK. Cytodiagnostic pitfalls in pulmonary coccidioidomycosis. Diagn Cytopathol 1995;12:177-180.
Chen KTK. Cytology of allergic bronchopulmonary aspergillosis. Diagn Cytopathol 1993;9:82-85.
Chow LTC, et al. Pulmonary sclerosing haemangioma. Report of a case with diagnosis by fine needle aspiration. Acta Cytol 1992;36:287-291.
Crosby JH, et al. Transthoracic fine needle aspiration of primary and metastatic sarcomas. Diagn Cytopathol 1985;1:221-227.
Dail DH. Uncommon tumours. In Pulmonary Pathology. Edited by DH Dail, SP Hammar. New York, Springer-Verlag 1988.
Daniel WC, et al. Light and electron microscopic observations of blastomyces dermatitidis in sputum. Acta Cytol 1979;23:222-226.
Das DK, et al. Ultrasound guided fine needle aspiration cytology: Diagnosis of hydatid disease of the abdomen and thorax. Diagn Cytopathol 1995;12:173-176.
Davenport RD. Diagnostic value of crush artefact in cytologic specimens. Occurrence in small cell carcinoma of the lung. Acta Cytol 1990;34:502-504.
Duggan MA, et al. Pulmonary cytology of the acquired immune deficiency syndrome: an analysis of 36 cases. Diagn Cytopathol 1986;2:181-186.
Dugan JM, et al. Diagnosis of pneumocystis carinii pneumonia by cytologic evaluation of papanicolaou stained bronchial specimens. Diagn Cytopathol 1988;4:106-11.
Dunbar F, Leiman G. The aspiration cytology of pulmonary hamartomas. Diagn Cytopathol 1989;5:174-180.
Fleury J, et al. Cell population obtained by bronchoalveolar lavage in pneumocystis carinii pneumonia. Acta Cytol 1985;29:721-726.
Flint A, Lloyd RV. Colon carcinoma metastatic to the lung. Cytologic manifestations and distinction from primary pulmonary adenocarcinoma. Acta Cytol 1992;36:230-235.
Garcia LS, et al. Sinus tract extension of a liver hydatid cyst and recovery of diagnostic hooklets in sputum. Am J Clin Pathol 1986;85:519-521.
Garret M, et al. Cytologic diagnosis of echinococcosis. Acta Cytol 1977;21:553-554.
Ghali VS, et al. Fluorescence of pneumocystis carinii in papanicolaou smears. Human Pathol 1984;15:907-909.
Gordon SM, et al. Diagnosis of pulmonary toxoplasmosis by bronchoalveolar lavage in cardiac transplant recipients. Diagn Cytopathol 1993;9:650-654.
Grotte D, et al. Reactive type II pneumocytes in bronchoalveolar lavage fluid from adult respiratory distress syndrome can be mistaken for cells of adenocarcinoma. Diagn Cytopathol 1990;6:317-322.
Guglietti, et al. The detection of coccidioides immitis in pulmonary cytology. Acta Cytol 1968;12:332-334.
Guglietti LC, Reingold IM. The detection of coccidioides immitis in pulmonary cytology. Acta Cytol 1968;12:332-334.
Gupta RK. Diagnosis of unsuspected pulmonary cryptococcosis with sputum cytology. Acta Cytol 1985;39:154-156.
Harding SA, et al. Pulmonary infection with capsule-deficient cryptococcus neoformans. Virchows Arch (A) 1979;382:113-118.
Hammar SP, et al. Ultrastructural and immunohistochemical features of common lung tumours: an overview. Ultra Pathol 1985;9:283-318.
Hammar SP. Common Neoplasms. In: Pulmonary Pathology. Edited by DH Dail, SP Hammar. New York, Springer-Verlag 1988.
Johnston WW, Amatulli J. The role of cytology in the primary diagnosis of North American blastomycosis. Acta Cytol 1970;14:200-204.
Johnston WW, Elson CE. Respiratory Tract. In: Comprehensive Cytopathology. Edited by M Bibbo. WB Saunders Company, Philadelphia 1991.
Johnston WW, Frable WJ. Diagnostic Respiratory Cytopathology. Paris, Masson 1979.
Johnston WW. Pleural fluid. Diagnositic Cytology Seminar, 23rd Annual Scientific Meeting. Acta Cytol 1976;20:428-43.
Kaplan W, Kraft DE. Demonstration of pathogenic fungi in formalin fixed tissues by immunofluorescence. Am J Clin Pathol 1969;52:420-432.
Kawahara, et al. Fine needle aspiration biopsy of primary malignant fibrous histiocytoma of the lung. Acta Cytol 1988;32:226-230.
Kim K, et al. Fine needle aspiration cytology of sarcomas metastatic to the lung. Acta Cytol 1986;30:688-694.
Kwon-Chung KJ, et al. New special stain for histopathological diagnosis of cryptococcosis. J Clin Microbiol 1981;13:383-387.
Lachman MF. Morphometric comparison of a metastatic transitional cell carcinoma simulating squamous metaplasia in sputum cytology. A case report. Acta Cytol 1994;38:407-409.
Lee JT, et al. Malignant fibrous histiocytoma of lung: A clinicopathologic and ultrastructural study of 5 cases. Cancer 1984;54:1124-1130.
Leong ASY, Gown AM. Immunohistochemistry of 'solid' tumours: poorly differentiated round cell and spindle cell tumours I. In: Applied Immunohistochemistry for the Surgical Pathologist. Edited by ASY Leong, Edward Arnold, London, 1993.
Louria DB, et al. Pulmonary mycetoma due to allescheria boydii. Arch Intern Med 1966;117:748-751.
Marchevsky AM, et al. The changing spectrum of disease, aetiology and diagnosis of mucormycosis. Hum Pathol 1980;11:457-464.
Maygarden SJ, Flanders EL. Mycobacteria can be seen as "negative images" in cytology smears from patients with acquired immunodeficiency syndrome. Mod Pathol 1989;2:239-243.
Murray PR, et al. The acid fast stain: a specific and predictive test for mycobacterial disease. Ann Intern Med 1980;92:512-513.
Naryshkin S, et al. Cytology of treated and minimal pneumocystis carinii pneumonia and a pitfall of the grocott methenamine silver stain. Diagn Cytopathol 1991;7:41-47.
Orell SR, et al. Manual and Atlas of fine needle aspiration cytology. Churchill Livingston, London 1992.
Orenstein M, et al. Cytologic diagnosis of pneumocystis carinii infection by bronchoalveolar lavage in acquired immune deficiency syndrome. Acta Cytol 1985;29:727-731.
Rosen SE, Koprowska I. Cytologic diagnosis of a case of pulmonary cryptococcosis. Acta Cytol 1982;26:499-502.
Rosenthal DL. Cytopathology of pulmonary disease. In: Monographs in Clinical Cytology. Edited by GL Wied. Basel, Karger SH 1988.
Saito Y, et al. Cytologic study of tissue repair in human bronchial epithelium. Acta Cytol 1988;32:622-628.
Silverman JF, et al. Negative image due to clofazimine crystals simulating MAI infection in a bronchoalveolar lavage specimen. Diagn Cytopathol 1993;9:534-540.
Silverman JF. Respiratory tract cytology including FNA. In: Atlas of Diagnositic Cytopathology. Edited by B. Atkinson. Philadephia, WB Saunders 1992.
Silverman JF, Johnsrude IS. Fine needle aspiration cytology of granulomatous cryptococcosis of the lung. Acta Cytol 1985;29:157-161.
Singh G, et al. Carcinoma of type II pneumocytes: PAS staining as a screening test for nuclear inclusions of surfactant - specific apoprotein. Cancer 1982;50:946- 948.
Stanley MW, et al. Pulmonary aspergillosis: an unusual cytologic presentation. Diagn Cytopathol 1992;8:585-587.
Walker WP, et al. Paranuclear blue inclusions in small cell undifferentiated carcinoma: a diagnostically useful finding demonstrated in fine needle aspiration biopsy smears. Diagn Cytopathol 1994;10:212-215.
Walloch JL, et al. Effects of therapy on cytologic specimens. In: Bibbo M, ed. Comprehensive Cytopathology. Philadelphia, WB Saunders 1991.
Watts JC, Chandler FW. Pneumocystic carinii pneumonitis: the nature and diagnostic significance of the methenamine silver-positive "intracystic bodies". Am J Surg Pathol 1985;9:744-751.