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THE SURGICAL TREATMENT OF ISOLATED PULMONARY CRYPTOCOCCOSIS
THE SURGICAL T R E A T M E N T OF ISOLATED PULMONARY
CRYPTOCOCCOSIS
]ames P. Lester, M.D., John C. Lane,
M.D.,
William H. Kern, M.D., and ]ohn C. Jones, M.D., Los Angeles, Calif.
C
known also as torulosis or European blastomycosis, is a mycotic disease of man and animals caused by Cryptococcus neoformans. The fungus appears in infected tissues or exudates as an ovoid or spherical single-budding, thick-walled, yeast-like organism, 5 to 20 microns in diameter. It is characterized by a wide gelatinous capsule which can be demonstrated clearly with India ink. 3,19 Unlike coccidioidomycosis and histoplasmosis, cryptococcosis is not limited geographically and reports of this disease have come from nearly all regions of the globe. It is thought to become air-borne from a reservoir in the soil, and may be disseminated hematogenously from the lungs to any part of the body. This fungus has a special predilection for the brain and meninges where it is ordinarily fatal within a period of 6 months. 19 ' 24 In its early stages, the disease is often confined to the lungs, and the patients are frequently entirely asymptomatic or may have nonspecific symptoms such as cough, hemoptysis, and vague chest discomfort. It is during this time that the prognosis is very favorable if operation is performed. Because of the lack of a dependable skin test, characteristic pulmonary symptoms, and specific radiographic findings, and because cultures may not be available before the patient undergoes therapy, most cases are diagnosed either after operation or at autopsy. Since early ade quate surgical therapy may achieve cures, the possibility of cryptococcosis should therefore be considered in the case of isolated or localized persistent pulmonary infiltrative lesions or circumscribed nodules, either calcified or not, which cannot be diagnosed by the usual methods. BYPTOCOCCOSIS,
CASE REPORTS CASE 1.—A 48-year-old Caucasian woman was seen in consultation at the Alhambra Community Hospital on Sept. 28, 1959, with a history of left lower chest pain of approxi mately one month's duration. The diagnostic impression was atelectasis of the left lower lobe. At the time the patient was received on our service, she had been hospitalized for approximately one month and had received many antibiotics. Subsequent bronchoscopy was normal and bronchography demonstrated an atelectatic left lower lobe with bronehiectasis in this area. A thoracentesis was performed with the removal of approximately 100 e.c. of bloody fluid which was sterile on culture and negative for malignant cells. Sputa and gastric lavage were negative on smear and culture for acid-fast bacilli. Physical examination revealed From the Departments of Surgery and Pathology, The Hospital of the Good Samaritan, and The University of Southern California, School of Medicine, Los Angeles, Calif. Received for publication Oct. 2, 1961. 207
L E S T E R E T AL.
208
J. Thoracic and Cardiovas. Surg.
only dullness and decreased breath sounds a t the base of the left lung. Skin tests for coceidioidomycosis and histoplasmosis were negative. A tuberculin skin test was positive. Chest films revealed pleural effusion at the base of the left lung with pleural reaction (Fig. 1 ) . A hemogram was unremarkable. The patient was discharged from the hospital on treatment with one of the tetracyclines, and was re-admitted J a n . 7, 1960. At this time the only symptom was vague discomfort in the left ehest. X-ray examination revealed little change in the lesion. On J a n . 8, 1960, a left lower lobectomy was performed. The gross appearance of the lesion was that of an unresolved pneumonia, and several smaller foci of necrosis were seen near the pleural surface along the base of the lobe. At the time of operation, a frozen section was suggestive and the final pathologic examination was diagnostic of cryptococcosis. The patient has remained asymptomatic through June of 1961.
Fig. 1.—Case 1.
Posteroanterior roentgenot'ram of ch'jit. Lurt pleural effusion and inflltrative lesion of left lower lobe. CASE 2.—A 41-year-old Caucasian man was admitted to the Hospital of the Good Samari tan on Oct. 25, 1960, with a history of intermittent left anterior chest pain for several years and sporadic hemoptysis and pleuritic pain of 5 weeks' duration. Physical examination was not remarkable. X-ray examination of the chest (Fig. 2) revealed a poorly circumscribed 6 to 7 em. lesion in the left upper lobe. Laryngoscopy and bronchoscopy were normal. Bron chial washings were negative for malignant cells. A hemogram on admission was normal. At thoraeotomy, on Nov. 1, 1960, the pleural surfaces were normal and a 6 to 7 cm. lesion was felt in the anterior segment of the left upper lobe adjacent to the lingula. Some dimpling of the pleural surface was noted. The regional lymph nodes were not remarkable. A left upper lobectomy was performed. The gross appearance of the involved area suggested either a pneumonitis or bronchiolar carcinoma (Fig. 3 ) . Pathologic examination demonstrated Cryptoooccus neoformans. I n one of the final sections, several small blood vessels were seen to contain organisms suggesting the possibility of systemic disease. This patient has remained asymptomatic through June, 1961, for a period of 8 months. PATHOLOGIC FEATURES
The lesions observed in both of our specimens were large, each measuring approximately 8 cm. in greatest diameter, and in both cases there were poorly
Vol. 44, No. 2 August, 1962
Fig. 2.—Case 2.
Fig. 3.—Case 2.
ISOLATED PULMONARY CRYPTOCOCCOSIS
209
Posteroanterior roentgenogram of chest which shows persistent infiltrate in left mid-lung field.
Left upper lobe showing the poorly circumscribed area of involvement.
LESTER ET AL.
210
J. Thoracic and Cardiovas. Surg.
defined separate foci of the disease in the adjacent parenchyma of the involved lobe. In the first case, there was a distinct but irregularly shaped area of necrosis, grossly resembling an abscess, and in this case the lesion was generally firmer and more fibrosed. In the second case, the gross appearance was char acterized by a granular, in areas gelatinous, appearance which was not unlike that seen in cases of bronchiolar carcinoma (see Fig. 3). The microscopic findings corresponded to this gross appearance, the lesion in the first case being characterized by extensive fibrosis between areas of necrosis and granulomatous inflammation (Fig. 4). In the second case, which was characterized by softer
Fig. 4.—Case 1.
Granulomatous inflammatory reaction.
texture and a gelatinous appearance, there was no significant fibrosis, and there was only a scanty cellular exudate within the alveoli, large numbers of oc casionally budding yeast-like fungi, characteristic of C. neoformans, being found free within the air sacs and within the interstitial tissue (Fig. 5). Similar but less numerous organisms were seen within the necrotie tissue and the granu lomatous lesions of the -first specimen. The organisms varied in size from 3 to 15 microns, and many were surrounded by thick, partially refractile, capsules. They stained prominently with PAS and Gomori methenamine silver stains. The wet mounts and India ink preparations from the second case, as well as the cultures, demonstrated characteristic C. neoformcms, whereas the cultures from the first case which was histologically also characteristic failed to demon strate specific growth. The described gross and microscopic findings of our 2
Vol. 44, No. 2 August, 1962
ISOLATED PULMONARY CEYPTOCOCCOSIS
211
cases correspond to the two types of pulmonary inflammatory reactions seen in cryptococcosis, namely, a granulomatous lesion or, more commonly, a grossly gelatinous lesion which is microscopically characterized by a relative lack of inflammatory cells. This is also the most common histologic appearance of the tumor in other organs, particularly the brain. 3 While the diagnosis can usually be made without difficulty, based on the characteristic bacteriologic findings, these findings may not be immediately available, or, for a variety of reasons, particularly preceding treatment with amphotericin B, the cultures may remain negative.15 In these cases, the original diagnosis must be based on the histologic
Fig. 5.—Case 2.
Numerous O. neoformana organisms in alveoli, without significant inflamma tory reaction.
appearance of the organisms in tissues, and, whenever possible, on their demon stration by frozen section as in Case 2. When yeast-like fungi are demonstrated in the sections, the possibility of blastomycosis, histoplasmosis, and coccidioidomycosis must be excluded. The most helpful morphologic findings are the thick gelatinous capsule and the occasional budding of the cryptococcus with the associated lack of severe inflammatory reaction. In blastomycosis, the organisms are also thick walled, but they are more uniform in size, being usually larger and measuring from 8 to 20 microns in diameter. Budding is more frequently found, and the organisms are always present in areas of inflammation with polymorphonuclear leukocytes and histiocytes, with or without giant cells, and often in areas of suppuration. In histoplasmosis, the organisms are smaller
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Vol. 44, No. 2
ISOLATED PULMONARY CKYPTOCOCCOSIS
213
August, 1962
(2 to 5 microns), quite uniform in size and shape, oval or spherical, with a clear halo, and they are uniformly within the cytoplasm of histiocytes. Inflam mation is always present and is essentially a granuloma with coagulation ne crosis, imitating tuberculosis. In coccidioidomycosis, the organisms vary widely in size, from 5 to 50 microns, the larger one having thick walls and showing evidence of endospore formation. 14 TREATMENT
Only approximately 300 cases of cryptococcosis have been reported in the world literature, but the National .Office of Vital Statistics recorded 151 fatal cases in the United States alone in the 4 year period after 1949, and 10 per cent of the 300 to 400 mycoses reported annually in the United States are caused by Cryptococcus neoformans. Because of this not insignificant number of cases and because of the high mortality rate in the disseminated form of the disease, early and adequate treatment of cryptococcosis while it is still localized in the lung is of great importance. In order to evaluate the results of the surgical treatment of cryptococcosis, we tabulated the cases of "clean pulmonary resec tions" reported throughout the world literature through December, 1960, ex cluding those cases in which the symptoms suggested meningeal involvement preoperatively, or those in which C. neoformans was in the cerebrospinal fluid immediately after operation. 6 ' r> 16>20'22> 23<27 Although we had excluded these cases except for reference, it is obvious that surgery should not be denied this group of patients since survival with meningeal involvement at the time of operation has been reported as long as 10 years postoperatively. 20 Two cases of spontaneous remission of pulmonary cryptococcosis have also been observed. 13 ' 18 From Table I, it may be seen that the treatment of isolated pulmonary cryptococcosis was usually a lobectomy or a wedge resection. Regardless of the extent of the resection, whether it be a wedge resection or a lobectomy, it should adequately encompass the lesion. The reported data would indicate that a wedge resection is often satisfactory from the standpoint of survival and preferential from the standpoint of preservation of lung tissue, but it is evident from our own experience that satellite areas of involvement may be present in the lung. Such lesions, when not excised with the major lesion, may well lead to eventual recurrence and dissemination. The data published by Palmrose and Losli23 and by Dormer 7 indicate that enucleation, partial excision, or needling of the lesions is inadvisable. While central nervous system involvement at the time of original diagnosis is usually, if not necessarily, suggestive of a fatal outcome and might best be evaluated by cerebrospinal fluid examinations, the presence of pleural effusion per se does not preclude the performance of a clean resection as shown by a case of Berk and Gerstle 1 in which the patient remained well 14 years postoperatively, and by one of ours who has remained well for 18 months. The follow-up study of these patients should be a long one, since subsequent deaths from central nervous system involvement have been reported,*' r ' 2 3 ' 2 7 but all of these patients had central nervous system symptoms prior to, or at the time of, operation, and for this reason were not included in our survey. In
L E S T E R E T AL.
214
J. Thoracic and Cardiovas. Surg.
all reported cases in which the resection could be performed for isolated pulmo nary cryptococeosis, the reported follow-up studies, frequently supplemented by personal notes from the authors, were uneventful, and there were no re ported cases of subsequent recurrence or dissemination. These results were obtained without treatment with any of the more recent anti-fungal agents, but some of the patients were treated with antituberculous drugs, potassium iodide, undecylenic acid, and antibiotics. Most of the patients were young adults, the range being from 15 to 62 years, and the disease presented in all lung fields, with no particular preference, but these factors did not appear to be important in the over-all favorable outcome. SUMMARY
Cryptococeosis is a mycotic disease of world-wide distribution having a special predilection for the brain and meninges, where it is ordinarily fatal within a period of 6 months. The disease is usually disseminated hematogenously from a primary focus in the lungs. Two cases in which isolated pul monary lesions were resected are reported, and 32 additional cases are reviewed. In cases in which there is no evidence of central nervous system involvement, lobectomy prevents the occurrence of fatal, disseminated disease and is the treatment of choice. The possibility of pulmonary crytococcosis should therefore be considered in cases of isolated or localized persistent pulmonary infiltrative lesions. REFERENCES 1. Berk, M., and Gerstle, B . : Torulosis (Cryptococeosis) Producing a Solitary Pulmonary Lesion, J . A. M. A. 149: 1310-1312, 1952. 2. Berk, M.: Personal communication to the authors, December, 1960. 3. Conant, N . F . , et al.: Manual of Clinical Mycology, ed. 2, Philadelphia and London, 1954, W. B. Saunders Company, pp. 149-168. 4. Corpe, R. F., and Parr, L. H . : Pulmonary Torulosis Complicating Pulmonary Tuberculosis Treated by Resection, J . THORACIC SURG. 2 7 : 392-398, 1954.
5. Corpe, R. F . : Personal communication to the authors, December, 1960. 6. Cruikshank, D. B., and Harrison, G. K . : A Case of Pulmonary Cryptococeosis, Thorax 7: 182-184, 1952. 7. Dormer, B . A., Friedlander, J., Wiles, F . J., and Simson, F . W . : Tumor of the Lung Due to Cryptocoeeus Histolyticus, J . THORACIC SURG. 14: 322-329, 1945.
8. Ellis, F . H . : Personal communication to the authors, December, 1960. 9. Froio, G. F . , and Bailey, C. P . : Pulmonary Cryptococeosis: Report of a Case With Surgical Cure, Dis. Chest 16: 354, 1949. 10. Haugen, R. K., and Baker, R. D . : Pulmonary Lesions in Cryptococeosis With Special Reference to Subpleural Nodules, Am. J . Clin. Path. 24: 1381-1390, 1954. 11. Haugen, R. K . : Personal communication to the authors, December, 1960. 12. Jacobs, L. G.: Personal communication to the authors, December, 1960. 13. Jensen, A. F . K . : Cryptococeosis, Nord. Med. 27: xl, 1958. 14. Kernohan, J . W.: Cancer Seminar, 2 : 73-76, 1957. 15. Katz, R. I., Birnbaum, H., and Eckmann, B . H . : Resection of Pulmonary Cryptococeosis Associated With Meningitis: Report of a Case. (To be Published.) 16. Khan, M. J., Meyers, R., and Koshi, G.: Pulmonary Cryptococeosis, Dis. Chest 36: 656, 1959. 17. Kuykendall, S. J., Ellis, F . H., Weed, L. A., and Donoghue, F . E . : Pulmonary Crypto coceosis, New England J . Med. 257: 1009-1016, 1957. 18. Linden, I . H . : Pulmonary Cryptococeosis, Am. Rev. Tubere. 69: 116-120, 1954. 19. Littman, M. L., and Zimmerman, L. E . : Cryptococeosis (Torulosis), New York, 1956, Grune & Stratton, Inc. 20. McConchie, I . : Torula Granuloma of the Lung, M. J . Australia 2 : 685-686, 1951. 21. MeConehie, I . : Personal communication to the authors, December, 1960.
Vol. 44, No. 2 August, 1962
ISOLATED PULMONARY CRYPTOCOCCOSIS
215 *±0
22. Meyers, R. M.: Personal communication, to the authors, December, 1960. 23. Palmrose, E . C , and Losli, E . J . : Cryptococcus Meningitis, Northwest Med. 5 1 : 121-126, 1952. 24. Poppe, J . K . : Cryptococcosis of the Lung, J . THORACIC SURG. 27: 608-613, 1954. 25. Poppe, J . K . : Personal communication to the authors, December, 1960. 26. Starr, K. W., and Geddes, B . : Pulmonary Torulosis, Australian & New Zealand J . Surg. 18: 212-214, 1949. 27. Susman, M. P . : Torula (Cryptococcus) Infection of the Lung, Australian & New Zealand J . Surg. 2 3 : 296-299, 1954. 28. White, M., Arany, L. S., and Jacobs, L. G.: Resection in Pulmonary Cryptococcosis (Torulosis), J . THORACIC SURG. 35: 402-410, 1958.
29. Webb, W. R., and Biggs, R. H . : Pulmonary Cryptococcosis, Dis. Chest 30: 659-668, 1956. 30. Webb, W. R.: Personal communication to the authors, December, 1960.
CRYPTOCOCCOSIS
]ames P. Lester, M.D., John C. Lane,
M.D.,
William H. Kern, M.D., and ]ohn C. Jones, M.D., Los Angeles, Calif.
C
known also as torulosis or European blastomycosis, is a mycotic disease of man and animals caused by Cryptococcus neoformans. The fungus appears in infected tissues or exudates as an ovoid or spherical single-budding, thick-walled, yeast-like organism, 5 to 20 microns in diameter. It is characterized by a wide gelatinous capsule which can be demonstrated clearly with India ink. 3,19 Unlike coccidioidomycosis and histoplasmosis, cryptococcosis is not limited geographically and reports of this disease have come from nearly all regions of the globe. It is thought to become air-borne from a reservoir in the soil, and may be disseminated hematogenously from the lungs to any part of the body. This fungus has a special predilection for the brain and meninges where it is ordinarily fatal within a period of 6 months. 19 ' 24 In its early stages, the disease is often confined to the lungs, and the patients are frequently entirely asymptomatic or may have nonspecific symptoms such as cough, hemoptysis, and vague chest discomfort. It is during this time that the prognosis is very favorable if operation is performed. Because of the lack of a dependable skin test, characteristic pulmonary symptoms, and specific radiographic findings, and because cultures may not be available before the patient undergoes therapy, most cases are diagnosed either after operation or at autopsy. Since early ade quate surgical therapy may achieve cures, the possibility of cryptococcosis should therefore be considered in the case of isolated or localized persistent pulmonary infiltrative lesions or circumscribed nodules, either calcified or not, which cannot be diagnosed by the usual methods. BYPTOCOCCOSIS,
CASE REPORTS CASE 1.—A 48-year-old Caucasian woman was seen in consultation at the Alhambra Community Hospital on Sept. 28, 1959, with a history of left lower chest pain of approxi mately one month's duration. The diagnostic impression was atelectasis of the left lower lobe. At the time the patient was received on our service, she had been hospitalized for approximately one month and had received many antibiotics. Subsequent bronchoscopy was normal and bronchography demonstrated an atelectatic left lower lobe with bronehiectasis in this area. A thoracentesis was performed with the removal of approximately 100 e.c. of bloody fluid which was sterile on culture and negative for malignant cells. Sputa and gastric lavage were negative on smear and culture for acid-fast bacilli. Physical examination revealed From the Departments of Surgery and Pathology, The Hospital of the Good Samaritan, and The University of Southern California, School of Medicine, Los Angeles, Calif. Received for publication Oct. 2, 1961. 207
L E S T E R E T AL.
208
J. Thoracic and Cardiovas. Surg.
only dullness and decreased breath sounds a t the base of the left lung. Skin tests for coceidioidomycosis and histoplasmosis were negative. A tuberculin skin test was positive. Chest films revealed pleural effusion at the base of the left lung with pleural reaction (Fig. 1 ) . A hemogram was unremarkable. The patient was discharged from the hospital on treatment with one of the tetracyclines, and was re-admitted J a n . 7, 1960. At this time the only symptom was vague discomfort in the left ehest. X-ray examination revealed little change in the lesion. On J a n . 8, 1960, a left lower lobectomy was performed. The gross appearance of the lesion was that of an unresolved pneumonia, and several smaller foci of necrosis were seen near the pleural surface along the base of the lobe. At the time of operation, a frozen section was suggestive and the final pathologic examination was diagnostic of cryptococcosis. The patient has remained asymptomatic through June of 1961.
Fig. 1.—Case 1.
Posteroanterior roentgenot'ram of ch'jit. Lurt pleural effusion and inflltrative lesion of left lower lobe. CASE 2.—A 41-year-old Caucasian man was admitted to the Hospital of the Good Samari tan on Oct. 25, 1960, with a history of intermittent left anterior chest pain for several years and sporadic hemoptysis and pleuritic pain of 5 weeks' duration. Physical examination was not remarkable. X-ray examination of the chest (Fig. 2) revealed a poorly circumscribed 6 to 7 em. lesion in the left upper lobe. Laryngoscopy and bronchoscopy were normal. Bron chial washings were negative for malignant cells. A hemogram on admission was normal. At thoraeotomy, on Nov. 1, 1960, the pleural surfaces were normal and a 6 to 7 cm. lesion was felt in the anterior segment of the left upper lobe adjacent to the lingula. Some dimpling of the pleural surface was noted. The regional lymph nodes were not remarkable. A left upper lobectomy was performed. The gross appearance of the involved area suggested either a pneumonitis or bronchiolar carcinoma (Fig. 3 ) . Pathologic examination demonstrated Cryptoooccus neoformans. I n one of the final sections, several small blood vessels were seen to contain organisms suggesting the possibility of systemic disease. This patient has remained asymptomatic through June, 1961, for a period of 8 months. PATHOLOGIC FEATURES
The lesions observed in both of our specimens were large, each measuring approximately 8 cm. in greatest diameter, and in both cases there were poorly
Vol. 44, No. 2 August, 1962
Fig. 2.—Case 2.
Fig. 3.—Case 2.
ISOLATED PULMONARY CRYPTOCOCCOSIS
209
Posteroanterior roentgenogram of chest which shows persistent infiltrate in left mid-lung field.
Left upper lobe showing the poorly circumscribed area of involvement.
LESTER ET AL.
210
J. Thoracic and Cardiovas. Surg.
defined separate foci of the disease in the adjacent parenchyma of the involved lobe. In the first case, there was a distinct but irregularly shaped area of necrosis, grossly resembling an abscess, and in this case the lesion was generally firmer and more fibrosed. In the second case, the gross appearance was char acterized by a granular, in areas gelatinous, appearance which was not unlike that seen in cases of bronchiolar carcinoma (see Fig. 3). The microscopic findings corresponded to this gross appearance, the lesion in the first case being characterized by extensive fibrosis between areas of necrosis and granulomatous inflammation (Fig. 4). In the second case, which was characterized by softer
Fig. 4.—Case 1.
Granulomatous inflammatory reaction.
texture and a gelatinous appearance, there was no significant fibrosis, and there was only a scanty cellular exudate within the alveoli, large numbers of oc casionally budding yeast-like fungi, characteristic of C. neoformans, being found free within the air sacs and within the interstitial tissue (Fig. 5). Similar but less numerous organisms were seen within the necrotie tissue and the granu lomatous lesions of the -first specimen. The organisms varied in size from 3 to 15 microns, and many were surrounded by thick, partially refractile, capsules. They stained prominently with PAS and Gomori methenamine silver stains. The wet mounts and India ink preparations from the second case, as well as the cultures, demonstrated characteristic C. neoformcms, whereas the cultures from the first case which was histologically also characteristic failed to demon strate specific growth. The described gross and microscopic findings of our 2
Vol. 44, No. 2 August, 1962
ISOLATED PULMONARY CEYPTOCOCCOSIS
211
cases correspond to the two types of pulmonary inflammatory reactions seen in cryptococcosis, namely, a granulomatous lesion or, more commonly, a grossly gelatinous lesion which is microscopically characterized by a relative lack of inflammatory cells. This is also the most common histologic appearance of the tumor in other organs, particularly the brain. 3 While the diagnosis can usually be made without difficulty, based on the characteristic bacteriologic findings, these findings may not be immediately available, or, for a variety of reasons, particularly preceding treatment with amphotericin B, the cultures may remain negative.15 In these cases, the original diagnosis must be based on the histologic
Fig. 5.—Case 2.
Numerous O. neoformana organisms in alveoli, without significant inflamma tory reaction.
appearance of the organisms in tissues, and, whenever possible, on their demon stration by frozen section as in Case 2. When yeast-like fungi are demonstrated in the sections, the possibility of blastomycosis, histoplasmosis, and coccidioidomycosis must be excluded. The most helpful morphologic findings are the thick gelatinous capsule and the occasional budding of the cryptococcus with the associated lack of severe inflammatory reaction. In blastomycosis, the organisms are also thick walled, but they are more uniform in size, being usually larger and measuring from 8 to 20 microns in diameter. Budding is more frequently found, and the organisms are always present in areas of inflammation with polymorphonuclear leukocytes and histiocytes, with or without giant cells, and often in areas of suppuration. In histoplasmosis, the organisms are smaller
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ISOLATED PULMONARY CKYPTOCOCCOSIS
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August, 1962
(2 to 5 microns), quite uniform in size and shape, oval or spherical, with a clear halo, and they are uniformly within the cytoplasm of histiocytes. Inflam mation is always present and is essentially a granuloma with coagulation ne crosis, imitating tuberculosis. In coccidioidomycosis, the organisms vary widely in size, from 5 to 50 microns, the larger one having thick walls and showing evidence of endospore formation. 14 TREATMENT
Only approximately 300 cases of cryptococcosis have been reported in the world literature, but the National .Office of Vital Statistics recorded 151 fatal cases in the United States alone in the 4 year period after 1949, and 10 per cent of the 300 to 400 mycoses reported annually in the United States are caused by Cryptococcus neoformans. Because of this not insignificant number of cases and because of the high mortality rate in the disseminated form of the disease, early and adequate treatment of cryptococcosis while it is still localized in the lung is of great importance. In order to evaluate the results of the surgical treatment of cryptococcosis, we tabulated the cases of "clean pulmonary resec tions" reported throughout the world literature through December, 1960, ex cluding those cases in which the symptoms suggested meningeal involvement preoperatively, or those in which C. neoformans was in the cerebrospinal fluid immediately after operation. 6 ' r> 16>20'22> 23<27 Although we had excluded these cases except for reference, it is obvious that surgery should not be denied this group of patients since survival with meningeal involvement at the time of operation has been reported as long as 10 years postoperatively. 20 Two cases of spontaneous remission of pulmonary cryptococcosis have also been observed. 13 ' 18 From Table I, it may be seen that the treatment of isolated pulmonary cryptococcosis was usually a lobectomy or a wedge resection. Regardless of the extent of the resection, whether it be a wedge resection or a lobectomy, it should adequately encompass the lesion. The reported data would indicate that a wedge resection is often satisfactory from the standpoint of survival and preferential from the standpoint of preservation of lung tissue, but it is evident from our own experience that satellite areas of involvement may be present in the lung. Such lesions, when not excised with the major lesion, may well lead to eventual recurrence and dissemination. The data published by Palmrose and Losli23 and by Dormer 7 indicate that enucleation, partial excision, or needling of the lesions is inadvisable. While central nervous system involvement at the time of original diagnosis is usually, if not necessarily, suggestive of a fatal outcome and might best be evaluated by cerebrospinal fluid examinations, the presence of pleural effusion per se does not preclude the performance of a clean resection as shown by a case of Berk and Gerstle 1 in which the patient remained well 14 years postoperatively, and by one of ours who has remained well for 18 months. The follow-up study of these patients should be a long one, since subsequent deaths from central nervous system involvement have been reported,*' r ' 2 3 ' 2 7 but all of these patients had central nervous system symptoms prior to, or at the time of, operation, and for this reason were not included in our survey. In
L E S T E R E T AL.
214
J. Thoracic and Cardiovas. Surg.
all reported cases in which the resection could be performed for isolated pulmo nary cryptococeosis, the reported follow-up studies, frequently supplemented by personal notes from the authors, were uneventful, and there were no re ported cases of subsequent recurrence or dissemination. These results were obtained without treatment with any of the more recent anti-fungal agents, but some of the patients were treated with antituberculous drugs, potassium iodide, undecylenic acid, and antibiotics. Most of the patients were young adults, the range being from 15 to 62 years, and the disease presented in all lung fields, with no particular preference, but these factors did not appear to be important in the over-all favorable outcome. SUMMARY
Cryptococeosis is a mycotic disease of world-wide distribution having a special predilection for the brain and meninges, where it is ordinarily fatal within a period of 6 months. The disease is usually disseminated hematogenously from a primary focus in the lungs. Two cases in which isolated pul monary lesions were resected are reported, and 32 additional cases are reviewed. In cases in which there is no evidence of central nervous system involvement, lobectomy prevents the occurrence of fatal, disseminated disease and is the treatment of choice. The possibility of pulmonary crytococcosis should therefore be considered in cases of isolated or localized persistent pulmonary infiltrative lesions. REFERENCES 1. Berk, M., and Gerstle, B . : Torulosis (Cryptococeosis) Producing a Solitary Pulmonary Lesion, J . A. M. A. 149: 1310-1312, 1952. 2. Berk, M.: Personal communication to the authors, December, 1960. 3. Conant, N . F . , et al.: Manual of Clinical Mycology, ed. 2, Philadelphia and London, 1954, W. B. Saunders Company, pp. 149-168. 4. Corpe, R. F., and Parr, L. H . : Pulmonary Torulosis Complicating Pulmonary Tuberculosis Treated by Resection, J . THORACIC SURG. 2 7 : 392-398, 1954.
5. Corpe, R. F . : Personal communication to the authors, December, 1960. 6. Cruikshank, D. B., and Harrison, G. K . : A Case of Pulmonary Cryptococeosis, Thorax 7: 182-184, 1952. 7. Dormer, B . A., Friedlander, J., Wiles, F . J., and Simson, F . W . : Tumor of the Lung Due to Cryptocoeeus Histolyticus, J . THORACIC SURG. 14: 322-329, 1945.
8. Ellis, F . H . : Personal communication to the authors, December, 1960. 9. Froio, G. F . , and Bailey, C. P . : Pulmonary Cryptococeosis: Report of a Case With Surgical Cure, Dis. Chest 16: 354, 1949. 10. Haugen, R. K., and Baker, R. D . : Pulmonary Lesions in Cryptococeosis With Special Reference to Subpleural Nodules, Am. J . Clin. Path. 24: 1381-1390, 1954. 11. Haugen, R. K . : Personal communication to the authors, December, 1960. 12. Jacobs, L. G.: Personal communication to the authors, December, 1960. 13. Jensen, A. F . K . : Cryptococeosis, Nord. Med. 27: xl, 1958. 14. Kernohan, J . W.: Cancer Seminar, 2 : 73-76, 1957. 15. Katz, R. I., Birnbaum, H., and Eckmann, B . H . : Resection of Pulmonary Cryptococeosis Associated With Meningitis: Report of a Case. (To be Published.) 16. Khan, M. J., Meyers, R., and Koshi, G.: Pulmonary Cryptococeosis, Dis. Chest 36: 656, 1959. 17. Kuykendall, S. J., Ellis, F . H., Weed, L. A., and Donoghue, F . E . : Pulmonary Crypto coceosis, New England J . Med. 257: 1009-1016, 1957. 18. Linden, I . H . : Pulmonary Cryptococeosis, Am. Rev. Tubere. 69: 116-120, 1954. 19. Littman, M. L., and Zimmerman, L. E . : Cryptococeosis (Torulosis), New York, 1956, Grune & Stratton, Inc. 20. McConchie, I . : Torula Granuloma of the Lung, M. J . Australia 2 : 685-686, 1951. 21. MeConehie, I . : Personal communication to the authors, December, 1960.
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22. Meyers, R. M.: Personal communication, to the authors, December, 1960. 23. Palmrose, E . C , and Losli, E . J . : Cryptococcus Meningitis, Northwest Med. 5 1 : 121-126, 1952. 24. Poppe, J . K . : Cryptococcosis of the Lung, J . THORACIC SURG. 27: 608-613, 1954. 25. Poppe, J . K . : Personal communication to the authors, December, 1960. 26. Starr, K. W., and Geddes, B . : Pulmonary Torulosis, Australian & New Zealand J . Surg. 18: 212-214, 1949. 27. Susman, M. P . : Torula (Cryptococcus) Infection of the Lung, Australian & New Zealand J . Surg. 2 3 : 296-299, 1954. 28. White, M., Arany, L. S., and Jacobs, L. G.: Resection in Pulmonary Cryptococcosis (Torulosis), J . THORACIC SURG. 35: 402-410, 1958.
29. Webb, W. R., and Biggs, R. H . : Pulmonary Cryptococcosis, Dis. Chest 30: 659-668, 1956. 30. Webb, W. R.: Personal communication to the authors, December, 1960.