Clinical Radiology(1992) 46, 292-294
Case Report: Complete Lung Collapse Presentation of Cryptococcosis E. A . C A R T E R ,
D. W. HENDERSON*,
J. M c B R I D E t
An Unusual
a n d M . R. S A G E
Departments of Radiology, *Histopathology and ~Microbiology, Flinders Medical Centre, Bedford Park, SA, Australia Cryptoeoccosis presenting as an intrabronchiai mass is not a recognized cause of complete lung collapse. This case report illustrates this extremely rare manifestation of pulmonary cryptococcosis, which mimicked primary pulmonary carcinoma clinically, radiologicaRy and bronehoscopically. C a r t e r , E . A . , H e n d e r s o n , D . W . , M c B r i d e , J. & S a g e , M . R . (1992). Clinical Radiology 46, 2 9 2 - 2 9 4 . C a s e R e p o r t : C o m p l e t e L u n g C o l l a p s e - A n U n u s u a l Presentation of Cryptococcosis
I n a n a d u l t , p r i m a r y l u n g c a r c i n o m a is a c o m m o n c a u s e o f lung collapse. However, significant volume loss, particul a r l y s e g m e n t a l c o l l a p s e is n o t a r e c o g n i z e d m a n i f e s t a t i o n of pulmonary cryptococcosis. This case illustrates the previously unreported occurrence of an intrabronchial mass leading to complete lung collapse.
CASE REPORT A 65-year-old man presented with a 3 month history of lethargy, weight loss, headache and a 3 week history of dyspnoea and cough, including haemoptysis. A chest X-ray showed left lower lobe consolidation and some volume loss and his local doctor treated him with antibiotics. He failed to improve and was admitted to hospital in respiratory distress, initially requiring ventilation. His chest X-ray on admission demonstrated complete left lung collapse with the left main bronchus terminating abruptly (Fig. 1). Two days later his chest X-ray showed reexpansion of the left upper lobe and a CT scan confirmed left lower lobe
Fig. 1 Complete left lung collapse with an abrupt end to the left main bronchus (arrows). Correspondence to: Dr E. A. Carter, Department of Radiology, Flinders Medical Centre, Bedford Park, South Australia 5042, Australia.
collapse with a hilar mass occluding the left lower lobe bronchus and narrowing the upper lobe bronchus, mimicking a primary lung cancer (Fig. 2). Bronehoscopy confirmed a mass lesion totally occluding the left lower lobe bronchus and partially occluding the left upper lobe bronchus, which was biopsied. The biopsy consisted of a single white fragment of tissue 3 mm in diameter. The surface was covered by a thin layer of metaplastic squamous epithelium. Nests of mildly atypical squamous cells intruded into the subjacent connective tissue, to produce the pattern of pseudoepitheliomatous hyperplasia (Fig. 3). Some of the cell nests showed central keratinization, and they were surrounded by an oedematous and focally vascular stroma, instead of the desmoplastic response expected in an invasive carcinoma. Numerous Cryptococcus organisms were present in the stroma, and some of the yeast-like fungal bodies showed evidence of budding. They were surrounded by a thick polysaccharide capsule, which was seen as a lucent halo in the haematoxylin and eosin (H&E)-stained sections, and which was stained intensely by the periodic acid-Schiff technique. The capsule was also identified by examination of sections stained with cresyl violet under polarized light [1]. In addition, the connective tissue contained a sparse inflammatory infiltrate, which was predominantly lymphocytic and plasmocytic in character. Cryptococcus neoformansvat gattii was subsequently isolated from cerebrospinal fluid and in material expressed from a 1 cm lesion on the left side of his neck. The serum cryptococcal antigen titre was 1 : 64. Haematological and biochemical parameters were normal and the HIV test was negative.
Fig. 2 - Chest CT (mediastinal windows) showing a left hilar mass (arrow) appearing to arise from and occluding the lower lobe bronchus with left lower lobe collapse. Small left pleural effusion. Narrowing of the left upper lobe bronchus was seen on the slice above (not shown).
COMPLETE LUNG COLLAPSE
293
Fig. 3 - First bronchial biopsy, showing the metaplastic squamous epithelium at the surface, and intrusive pseudoepitheliomatous nests of squamous cells within the subjacent oedematous connective tissue. H&E, x 80 (original magnification).
The patient's condition improved after airway patency was restored bronchoscopically. The follow-up biopsies from the bronchial disobliteration consisted o f very soft pink gelatinous translucent tissue, with the largest fragment measuring 17 x I0 x 7 mm. The histological appearances (Fig. 4) were identical to those of the first biopsy, except that the oedematous connective tissue containing cryptoeocci could be seen extending around bronchial cartilages. Electron microscopy also revealed the typical features of a Cryptococcus species [2]. The patient was commenced on Amphtericin B and Flucytosine. Mild renal impairment was noted during therapy and drug dosages were altered accordingly. Cerebrospinal fluid examination prior to discharge showed clearance of the cryptococci, at which time, the patient was asymptomatic and there was complete radiological resolution of the left lower lobe collapse. Further treatment with Flucouazole was then prescribed.
DISCUSSION Cryptococcosis is caused by the yeast-like fungus,
Cryptococcus neoformans, which has a world-wide distribution, with highest prevalence in the USA and Australia [3]. Infectious propagules of Cryptococcus neoformans var gattii have been demonstrated in association with flowering Eucalyptus camaldulensis (the river red gum) [4]. It is thought to be acquired by inhalation, but it is an uncommon pulmonary pathogen, most frequently recognized as an opportunistic infection in immunocompromised hosts (50-80%) particularly lymphohaematological disorders and more recently AIDS [3,5-7]. The infection is thought to result in a subpleural focus with spread to ipsilateral hilar lymph nodes, like tuberculosis, healing in most but disseminating in the immunocompromised and occasionally in the immunocompetent [7,8]. It often disseminates to the central nervous system and it most commonly presents as a meningitis, with the pulmonary infection often remaining subclinical [5-8] in which case there often is no chest X-ray abnormality due to healing of the lung lesion [9]. Calcification and scarring are rare [10].
Fig. 4 - Second bronchial biopsy. Numerous cryptococci are evident, and the capsules surrounding the central yeast-like body are shown (arrows). Diastase-periodic acid-Schiff, x 475 (original magnification).
Isolated pulmonary infection is only clinically recognized in 10% of all proven cryptococcal infections [5]. Symptoms are often mild, but haemoptysis is uncommon [5,9]. Symptoms are much more common in the immunocompromised, particularly with AIDS [7]. Asymptomatic colonization of the major airways can occur, mostly in patients with chronic pulmonary disease or lung cancer [101. Radiologically, it is typically seen as a single, welldefined mass, often pleurally based, multiple nodules or ill-defined consolidation, the latter being more common in the immunocompromised [10,11]. It often mimics primary or metastatic malignancy, as one or more pulmonary mass lesions. Particularly, where a single pulmonary nodule is associated with neurological symptoms, cryptococcosis may often be misinterpreted as primary lung carcinoma with cerebral metastases [12]. But there is only one previous report of consolidation with minor volume loss with radiological evidence of bronchial occlusion due to an intrabronchial gelatinous cryptococcal mass [13]. A case of right middle lobe consolidation with an obstructive defect later noted on spirometry and a granulomatous cryptococcal lesion within the carina partially obstructing both the right and left main bronchi, seen at bronchoscopy has also been reported [9]. There is also a report o f an anterior mediastinal toruloma compressing and infiltrating the
294
CLINICAL RADIOLOGY
trachea, right a n d left m a i n bronchi, a n d adjacent m e d i a s t i n a l a n d hilar structures [14]. Cavitation, a miliary pattern, a n d less so pleural effusions, hilar and m e d i a s t i n a l l y m p h a d e n o p a t h y are also u n c o m m o n radiological features, mostly seen in the i m m u n o c o m p r o m i s e d p a t i e n t [11]. D i s s e m i n a t e d disease m a y result i n a miliary p a t t e r n or multiple diffuse illdefined opacities and is associated with pleural effusions [10,11]. Collapse is thus a n extremely rare m a n i f e s t a t i o n o f p u l m o n a r y cryptococcosis, where clearly even consolidation with volume loss is u n c o m m o n . It m a y be secondary to extrinsic b r o n c h i a l c o m p r e s s i o n or a n i n t r a b r o n c h i a l cryptococcal mass as in this case. The b r o n c h i a l localization in this case, with m i m i c r y o f a central b r o n c h o g e n i c c a r c i n o m a clinically, radiologically a n d b r o n c h o s c o p i cally, p r o d u c i n g collapse of the left tung is extraordinary. M o s t cryptococcomas in i m m u n o c o m p e t e n t hosts are peripheral in location [3]. The appearances of the pseud o e p i t h e l i o m a t o u s hyperplasia in the b r o n c h i a l biopsies bore a close resemblance to the regenerative atypical s q u a m o u s metaplasia described by C h a d r a r a t n a m et al. [15] in sites of repeated b r o n c h i a l biopsies, a n d they were distinguishable from invasive s q u a m o u s c a r c i n o m a by: (1) the b l a n d a p p e a r a n c e o f the s q u a m o u s cells; (2) absence of the desmoplastic s t r o m a expected in a n invasive carcinoma; a n d (3) the presence of i n n u m e r a b l e C r y p t o c o c c u s organisms. Acknowledgements. We thank Mr M. Peacock for permission to report this case under his care. REFERENCES
1 Klatzko I, Geisler PH. Notes on technic: demonstration of Cryptococcus neoformans in polarized light. Stain Technology 1958;33:5556.
2 Wills EL Infectious agents. Fungi, bacteria and viruses. In: Papadimitriou, JM, Henderson, DW & Spagnolo, DV, eds. Diagnostic ultrastructure of non-neoplastic diseases. Edinburgh: Churchill Livingstone, 1991:157 202. 3 Chandler FW, Watts JC. Fungal infections.In: Dail DH & Hammer SP, eds. Pulmonary pathology. New York: Springer-Verlag, 1988:189 257. 4 Ellis DH, PfeifferTJ. Ecology, lifecycle, and infectiouspropagule of Cryptococcus neoformans. Lancet 1990;316:923 925. 5 Hatcher CR Jr, SehdevaJ, Waters WC III, SchulzeV, Logan WD Jr, Symbas P e t al. Primary pulmonary cryptococcosis. Journal of Thoracic and Cardiovascular Surgery 1971;61:39-49. 6 Miller WT Jr, Edelman JM, Miller WT. Cryptococcal pulmonary infection in patients with AIDS: radiographic appearance. Radiology 1990;175:725 728. 7 Wasser L, Talavera W. Pulmonary cryptococcosis in AIDS. Chest 1987;92:692 695. 8 Sayler WR, Salyer DC, Baker RD. Primary complex of Cryptococcus and pulmonary lymph nodes. Journal of Infectious Diseases 1974;130:74 77. 9 Town GI, Seemen R. Pulmonary cryptococcosis: a report of two cases and review of the literature. New Zealand Medical Journal 1985;98:894-895. 10 Fraser RG, Pare JAP, Pare PD, Fraser RS, Genereux GP. Diagnosis' of diseases of the chest, 3rd ed. Philadelphia: WB Saunders, 1989:975 985. 11 Khoury MB, Godwin JD, Ravin CE, Gallis HA, Halvorsen RA, Putman CE. Thoracic cryptococcosis: immunologic competence and radiologic appearance. American Journal of Radiology 1984;142:893-896. 12 Meighan JW. Pulmonary cryptococcosis mimicking carcinoma of the lung. Radiology 1972;103:61 62. 13 Long RF, Berens SV, Shambhag GR. Case reports. An unusual manifestation of pulmonary cryptococcosis. British Journal oJ Radiology 1972;45:757 759. 14 Sinha P, Naik KG, Bhagwat GP. Mediastinal cryptococcoma. Thorax 1978;33:657-659. 15 Chandraratnam EA, Henderson DW, Meredith DJ, Jain S. Regenerative atypical squamous metaplasia in fibreoptic bronchial biopsy sites - a lesion liable to misinterpretation as carcinoma on rebiopsy: report of 5 cases. Pathology 1987;19:419-424.
Case Report: Complete Lung Collapse Presentation of Cryptococcosis E. A . C A R T E R ,
D. W. HENDERSON*,
J. M c B R I D E t
An Unusual
a n d M . R. S A G E
Departments of Radiology, *Histopathology and ~Microbiology, Flinders Medical Centre, Bedford Park, SA, Australia Cryptoeoccosis presenting as an intrabronchiai mass is not a recognized cause of complete lung collapse. This case report illustrates this extremely rare manifestation of pulmonary cryptococcosis, which mimicked primary pulmonary carcinoma clinically, radiologicaRy and bronehoscopically. C a r t e r , E . A . , H e n d e r s o n , D . W . , M c B r i d e , J. & S a g e , M . R . (1992). Clinical Radiology 46, 2 9 2 - 2 9 4 . C a s e R e p o r t : C o m p l e t e L u n g C o l l a p s e - A n U n u s u a l Presentation of Cryptococcosis
I n a n a d u l t , p r i m a r y l u n g c a r c i n o m a is a c o m m o n c a u s e o f lung collapse. However, significant volume loss, particul a r l y s e g m e n t a l c o l l a p s e is n o t a r e c o g n i z e d m a n i f e s t a t i o n of pulmonary cryptococcosis. This case illustrates the previously unreported occurrence of an intrabronchial mass leading to complete lung collapse.
CASE REPORT A 65-year-old man presented with a 3 month history of lethargy, weight loss, headache and a 3 week history of dyspnoea and cough, including haemoptysis. A chest X-ray showed left lower lobe consolidation and some volume loss and his local doctor treated him with antibiotics. He failed to improve and was admitted to hospital in respiratory distress, initially requiring ventilation. His chest X-ray on admission demonstrated complete left lung collapse with the left main bronchus terminating abruptly (Fig. 1). Two days later his chest X-ray showed reexpansion of the left upper lobe and a CT scan confirmed left lower lobe
Fig. 1 Complete left lung collapse with an abrupt end to the left main bronchus (arrows). Correspondence to: Dr E. A. Carter, Department of Radiology, Flinders Medical Centre, Bedford Park, South Australia 5042, Australia.
collapse with a hilar mass occluding the left lower lobe bronchus and narrowing the upper lobe bronchus, mimicking a primary lung cancer (Fig. 2). Bronehoscopy confirmed a mass lesion totally occluding the left lower lobe bronchus and partially occluding the left upper lobe bronchus, which was biopsied. The biopsy consisted of a single white fragment of tissue 3 mm in diameter. The surface was covered by a thin layer of metaplastic squamous epithelium. Nests of mildly atypical squamous cells intruded into the subjacent connective tissue, to produce the pattern of pseudoepitheliomatous hyperplasia (Fig. 3). Some of the cell nests showed central keratinization, and they were surrounded by an oedematous and focally vascular stroma, instead of the desmoplastic response expected in an invasive carcinoma. Numerous Cryptococcus organisms were present in the stroma, and some of the yeast-like fungal bodies showed evidence of budding. They were surrounded by a thick polysaccharide capsule, which was seen as a lucent halo in the haematoxylin and eosin (H&E)-stained sections, and which was stained intensely by the periodic acid-Schiff technique. The capsule was also identified by examination of sections stained with cresyl violet under polarized light [1]. In addition, the connective tissue contained a sparse inflammatory infiltrate, which was predominantly lymphocytic and plasmocytic in character. Cryptococcus neoformansvat gattii was subsequently isolated from cerebrospinal fluid and in material expressed from a 1 cm lesion on the left side of his neck. The serum cryptococcal antigen titre was 1 : 64. Haematological and biochemical parameters were normal and the HIV test was negative.
Fig. 2 - Chest CT (mediastinal windows) showing a left hilar mass (arrow) appearing to arise from and occluding the lower lobe bronchus with left lower lobe collapse. Small left pleural effusion. Narrowing of the left upper lobe bronchus was seen on the slice above (not shown).
COMPLETE LUNG COLLAPSE
293
Fig. 3 - First bronchial biopsy, showing the metaplastic squamous epithelium at the surface, and intrusive pseudoepitheliomatous nests of squamous cells within the subjacent oedematous connective tissue. H&E, x 80 (original magnification).
The patient's condition improved after airway patency was restored bronchoscopically. The follow-up biopsies from the bronchial disobliteration consisted o f very soft pink gelatinous translucent tissue, with the largest fragment measuring 17 x I0 x 7 mm. The histological appearances (Fig. 4) were identical to those of the first biopsy, except that the oedematous connective tissue containing cryptoeocci could be seen extending around bronchial cartilages. Electron microscopy also revealed the typical features of a Cryptococcus species [2]. The patient was commenced on Amphtericin B and Flucytosine. Mild renal impairment was noted during therapy and drug dosages were altered accordingly. Cerebrospinal fluid examination prior to discharge showed clearance of the cryptococci, at which time, the patient was asymptomatic and there was complete radiological resolution of the left lower lobe collapse. Further treatment with Flucouazole was then prescribed.
DISCUSSION Cryptococcosis is caused by the yeast-like fungus,
Cryptococcus neoformans, which has a world-wide distribution, with highest prevalence in the USA and Australia [3]. Infectious propagules of Cryptococcus neoformans var gattii have been demonstrated in association with flowering Eucalyptus camaldulensis (the river red gum) [4]. It is thought to be acquired by inhalation, but it is an uncommon pulmonary pathogen, most frequently recognized as an opportunistic infection in immunocompromised hosts (50-80%) particularly lymphohaematological disorders and more recently AIDS [3,5-7]. The infection is thought to result in a subpleural focus with spread to ipsilateral hilar lymph nodes, like tuberculosis, healing in most but disseminating in the immunocompromised and occasionally in the immunocompetent [7,8]. It often disseminates to the central nervous system and it most commonly presents as a meningitis, with the pulmonary infection often remaining subclinical [5-8] in which case there often is no chest X-ray abnormality due to healing of the lung lesion [9]. Calcification and scarring are rare [10].
Fig. 4 - Second bronchial biopsy. Numerous cryptococci are evident, and the capsules surrounding the central yeast-like body are shown (arrows). Diastase-periodic acid-Schiff, x 475 (original magnification).
Isolated pulmonary infection is only clinically recognized in 10% of all proven cryptococcal infections [5]. Symptoms are often mild, but haemoptysis is uncommon [5,9]. Symptoms are much more common in the immunocompromised, particularly with AIDS [7]. Asymptomatic colonization of the major airways can occur, mostly in patients with chronic pulmonary disease or lung cancer [101. Radiologically, it is typically seen as a single, welldefined mass, often pleurally based, multiple nodules or ill-defined consolidation, the latter being more common in the immunocompromised [10,11]. It often mimics primary or metastatic malignancy, as one or more pulmonary mass lesions. Particularly, where a single pulmonary nodule is associated with neurological symptoms, cryptococcosis may often be misinterpreted as primary lung carcinoma with cerebral metastases [12]. But there is only one previous report of consolidation with minor volume loss with radiological evidence of bronchial occlusion due to an intrabronchial gelatinous cryptococcal mass [13]. A case of right middle lobe consolidation with an obstructive defect later noted on spirometry and a granulomatous cryptococcal lesion within the carina partially obstructing both the right and left main bronchi, seen at bronchoscopy has also been reported [9]. There is also a report o f an anterior mediastinal toruloma compressing and infiltrating the
294
CLINICAL RADIOLOGY
trachea, right a n d left m a i n bronchi, a n d adjacent m e d i a s t i n a l a n d hilar structures [14]. Cavitation, a miliary pattern, a n d less so pleural effusions, hilar and m e d i a s t i n a l l y m p h a d e n o p a t h y are also u n c o m m o n radiological features, mostly seen in the i m m u n o c o m p r o m i s e d p a t i e n t [11]. D i s s e m i n a t e d disease m a y result i n a miliary p a t t e r n or multiple diffuse illdefined opacities and is associated with pleural effusions [10,11]. Collapse is thus a n extremely rare m a n i f e s t a t i o n o f p u l m o n a r y cryptococcosis, where clearly even consolidation with volume loss is u n c o m m o n . It m a y be secondary to extrinsic b r o n c h i a l c o m p r e s s i o n or a n i n t r a b r o n c h i a l cryptococcal mass as in this case. The b r o n c h i a l localization in this case, with m i m i c r y o f a central b r o n c h o g e n i c c a r c i n o m a clinically, radiologically a n d b r o n c h o s c o p i cally, p r o d u c i n g collapse of the left tung is extraordinary. M o s t cryptococcomas in i m m u n o c o m p e t e n t hosts are peripheral in location [3]. The appearances of the pseud o e p i t h e l i o m a t o u s hyperplasia in the b r o n c h i a l biopsies bore a close resemblance to the regenerative atypical s q u a m o u s metaplasia described by C h a d r a r a t n a m et al. [15] in sites of repeated b r o n c h i a l biopsies, a n d they were distinguishable from invasive s q u a m o u s c a r c i n o m a by: (1) the b l a n d a p p e a r a n c e o f the s q u a m o u s cells; (2) absence of the desmoplastic s t r o m a expected in a n invasive carcinoma; a n d (3) the presence of i n n u m e r a b l e C r y p t o c o c c u s organisms. Acknowledgements. We thank Mr M. Peacock for permission to report this case under his care. REFERENCES
1 Klatzko I, Geisler PH. Notes on technic: demonstration of Cryptococcus neoformans in polarized light. Stain Technology 1958;33:5556.
2 Wills EL Infectious agents. Fungi, bacteria and viruses. In: Papadimitriou, JM, Henderson, DW & Spagnolo, DV, eds. Diagnostic ultrastructure of non-neoplastic diseases. Edinburgh: Churchill Livingstone, 1991:157 202. 3 Chandler FW, Watts JC. Fungal infections.In: Dail DH & Hammer SP, eds. Pulmonary pathology. New York: Springer-Verlag, 1988:189 257. 4 Ellis DH, PfeifferTJ. Ecology, lifecycle, and infectiouspropagule of Cryptococcus neoformans. Lancet 1990;316:923 925. 5 Hatcher CR Jr, SehdevaJ, Waters WC III, SchulzeV, Logan WD Jr, Symbas P e t al. Primary pulmonary cryptococcosis. Journal of Thoracic and Cardiovascular Surgery 1971;61:39-49. 6 Miller WT Jr, Edelman JM, Miller WT. Cryptococcal pulmonary infection in patients with AIDS: radiographic appearance. Radiology 1990;175:725 728. 7 Wasser L, Talavera W. Pulmonary cryptococcosis in AIDS. Chest 1987;92:692 695. 8 Sayler WR, Salyer DC, Baker RD. Primary complex of Cryptococcus and pulmonary lymph nodes. Journal of Infectious Diseases 1974;130:74 77. 9 Town GI, Seemen R. Pulmonary cryptococcosis: a report of two cases and review of the literature. New Zealand Medical Journal 1985;98:894-895. 10 Fraser RG, Pare JAP, Pare PD, Fraser RS, Genereux GP. Diagnosis' of diseases of the chest, 3rd ed. Philadelphia: WB Saunders, 1989:975 985. 11 Khoury MB, Godwin JD, Ravin CE, Gallis HA, Halvorsen RA, Putman CE. Thoracic cryptococcosis: immunologic competence and radiologic appearance. American Journal of Radiology 1984;142:893-896. 12 Meighan JW. Pulmonary cryptococcosis mimicking carcinoma of the lung. Radiology 1972;103:61 62. 13 Long RF, Berens SV, Shambhag GR. Case reports. An unusual manifestation of pulmonary cryptococcosis. British Journal oJ Radiology 1972;45:757 759. 14 Sinha P, Naik KG, Bhagwat GP. Mediastinal cryptococcoma. Thorax 1978;33:657-659. 15 Chandraratnam EA, Henderson DW, Meredith DJ, Jain S. Regenerative atypical squamous metaplasia in fibreoptic bronchial biopsy sites - a lesion liable to misinterpretation as carcinoma on rebiopsy: report of 5 cases. Pathology 1987;19:419-424.
