Cryptococcosis Michael C.
Reese, MD, Joe B. Colclasure,
of the MD
\s=b\ An unusual case of cryptococcosis of the larynx initially developed as an acute upper airway obstruction that necessitated tracheostomy. Concomitant findings were tracheobronchial ulcerations and edema with severe mainstem bronchial constriction on the left side. Budding "yeast-like organisms" that were consistent with Cryptococcus neoformans appeared in tissue specimens. Epithelial changes that were consistent with pseudoepitheliomatous hyperplasia occurred in areas in the immediate vicinity of the organisms. Sputum and bronchial washing cultures grew nonmycelial, mucinous, encapsulated forms that were positive to staining with mucicarmine and Alcian blue. Treatment with amphotericin B resulted in resolution of the laryngeal obstruction, permitting decannulation. Follow-up direct laryngoscopy and biopsy three months after completion of therapy revealed only mild edema of the false vocal folds. No organisms were found in the tissue, and the pseudoepitheliomatous hyperplastic mucosal changes had resolved.
(Arch Otolaryngol 101:698-701, 1975)
the past, microbiologists have been inconsistent about termi¬ nology and specific identification of the Cryptococcus neoformans orga¬ nism with respect to deep mycotic in-
In
Accepted
publication June 26, 1975. Department of Otolaryngology, University Hospital, Little Rock, Ark. Reprint requests to 1110 W Elm, Rogers, AR 72756 (Dr Reese). From the
for
Larynx
fections. For some time, the term "Torula" was inappropriately used to describe cryptococcosis. European blastomycosis and Busse-Buschke dis¬ ease are two of the various names for C neoformans infections.1 One refer¬ ence prior to 1940 considered Monilia, North American blastomycosis, and cryptococcosis to be members of the blastomycosis group. These factors lend confusion to interpretation of the earlier reports of laryngeal mycoses. A review of the literature reveals
several reports of suspected mycotic diseases of the larynx, but none could be found specifically incriminating C
neoformans.'2·3 Close scrutiny of proved cases of upper respiratory cryptococcosis re¬ veals that the disease is primarily pulmonary, with secondary involve¬ ment of other structures.4 Extra¬ is most com¬
pulmonary involvement
in the central nervous system, but involvement of the prostate, mon
spleen, liver, kidney, nasopharynx, paranasal sinuses, and nasal and oral lesions have also been reported.4-5 Cryptococcus neoformans infections
from inhalation of the orga¬ nisms that are found in pigeon and other avian solid excrements and soil. Infections caused by this organism have been thought to be present as an opportunist in patients with debili¬ tating systemic disease and in per¬ sons taking steroids or cytotoxic sub¬ stances." The disease in humans is not occur
contagious.
In a review of 220 cases of infec¬ tions with C neoformans, the central nervous system was involved in 81%, and the pulmonary system in 20%. These statistics indicate the transi¬ tory, mild, and frequently unrecog¬ nized nature of the pulmonary dis¬ ease. Hematogenous spread to other sites occurs mainly to the central ner¬ vous system. The frequent transitory nature of the pulmonary involvement is further elucidated by the fact that many proved cases of C neoformans of the lung are known to have healed spontaneously, leaving only the dis¬ seminated disease persisting. The pulmonary lesion heals by encapsula¬ tion, with no residual scar.1 With pulmonary involvement, the diagnosis is most commonly estab¬ lished by sputum exam. With extra¬ pulmonary disease, the diagnosis is made by identifying the organisms in the tissue. Cutaneous and mucous membrane involvement usually is a manifestation of disseminated infec¬ tion. Histopathologic differentiation is sometimes difficult, and the tissue form of C neoformans is frequently confused with Blastomyces dermatitidis. The mucopolysaccharide capsule is thick, and elicits a mild cellular re¬ action in tissue. This capsule charac¬ teristically stains with mucicarmine.7 Definitive identification of C neo¬ formans by culture must be made by the following criteria: (1) the orga-
Downloaded From: http://archotol.jamanetwork.com/ by a University of British Columbia Library User on 06/17/2015
Fig 2—Contrast laryngogram with edema of true and false vocal cords.
Fig 1 —Chest x-ray film disease.
on
admission. Paucity of
nism grows in mucoid colonies on the Sabouraud agar medium at 37 C; (2) culture grows encapsulated, nonmycelial yeast forms; (3) inability to fer¬ ment sugars; and (4) positive reaction
production tests.8 Complement fixation and direct fluorescent antibody tests have been to urease
unreliable. Our case is reported to describe the first known involvement of the larynx by C neoformans with resultant chronic airway obstruction and a sub¬ sequent acute respiratory emergency that required tracheostomy. REPORT OF A CASE A 47-year-old man was admitted to the University Hospital emergency room on Nov 29, 1973, with the chief complaint of gradual onset of hoarseness and dyspnea of two years' duration. On the day of ad¬ mission he had developed severe respira¬ tory distress that required tracheostomy. Within the previous two years prior to the onset of symptoms he had worked in
soil that had been treated with chicken ma¬ nure. During prior admissions to this hos¬ pital in 1970, diagnoses of exogenous obe¬ sity, hypertension of renal origin, chronic proteinuria, and arteriosclerotic heart dis¬ ease had been identified and evaluated by the Medicine Department. Classification of the organic heart disease was (1) arterio¬ sclerotic heart disease, (2) cardiomegaly, (3) probably congestive heart failure, and
(4)
radiographie
not
chronic
evidence of
pulmonary
drug-induced. The cause of proteinuria was not known.
his
Laboratory Findings Laboratory studies disclosed the follow¬ ing values: hemoglobin, 13.8 gm/100 ml; hematocrit, 39%; white blood cell (WBC) count, 5,800/cu mm with 70% neutrophils, 6% eosinophils, 10% lymphocytes, and 12% monocytes; platelet count, 251,000/cu mm; blood urea nitrogen, 57 mg/100 ml; serum creatinine, 4.7 mg/100 ml; and serum alka¬ line phosphatase, 58 King-Armstrong units/ 100 ml. The levels of serum electrolytes, se¬ rum glutamic oxaloacetic transaminase, serum bilirubin, serum cholesterol, and se¬ rum triglycérides were normal. The 24hour urine protein level was 46 gm, urine creatinine clearance was 88 ml/min, the se¬ protein level was 6.2 gm/100 ml, and the serum albumin level was 2.9 gm/100 ml. The latter values were determined on his previous admission. The direct fluores¬ cent antibody tube agglutination and latex agglutination tests for Crytococcus were rum
negative.
The blood gas values
prior
to tracheos¬
tomy were as follows: arterial oxygen pres¬
sure, 38 mm Hg; arterial carbon dioxide pressure, 32 mm Hg; pH, 7.490; H% 32; and HCO5, 23. The blood gas values after tra¬ cheostomy were as follows: arterial oxygen pressure, 60 mm Hg; arterial carbon diox¬ ide pressure, 35 mm Hg; pH, 7.410; H*, 38;
and
HCO3, 21.
Physical Examination Physical examination revealed
the fol-
lowing: blood pressure, 155/100 mm Hg; pulse rate was 84 beats per minute; respi¬ rations, 36/min; and rectal temperature, 36.7 C (98 F). Apparent signs and symp¬ toms of upper airway obstruction were present, along with expiratory and inspira¬ tory wheezes by auscultation of both lungs. Pitting edema (4 + ) of both feet was noted.
Radiographic Examination Chest x-ray film revealed cardiomegaly with left ventricular prominence, and a prominent right hilum. No infiltrates were seen (Fig 1). Tomograms of the right hilum revealed that no cavity was pres¬ ent. Sinus x-ray films and intravenous pyelograms were negative. A laryngogram revealed laryngeal edema involving epi¬ glottis and false and true vocal cords, with decreased mobility of the true vocal cords. There was asymmetry of the subglot¬ tic arches (Fig 2).
Additional
Findings
A spinal tap was performed on Nov 29, 1973. No WBCs or red blood cells were present. A VDRL test for syphilis was negative. An India ink preparation was negative, and a culture was negative for
growth.
Transnasal fiberoptic bronchoscopy re¬ vealed multiple punctate ulcers with white exudates involving the entire tracheobron¬ chial tree. Bronchial washings cultured C
neoformans.
Direct laryngoscopy and biopsy revealed marked laryngeal edema and glottic ob¬ struction, and multiple, white, raised exudative lesions of the mucosa. A biopsy specimen of the right false vocal cord was positive for a "yeast-like" organism con¬ sistent with C neoformans. On Nov 30, 1973, transtracheal fiberoptic bronchoscopy revealed scattered white plaques on the mucosa of the entire
Downloaded From: http://archotol.jamanetwork.com/ by a University of British Columbia Library User on 06/17/2015
tion failed to reveal any organisms in the tissue, and there was complete resolution of the pseudoepitheliomatous hyperplasia. The patient was last seen on March 16, 1975, in good health, with continuing im¬ provement in the quality of his voice.
COMMENT
The classic example of a debilitated patient being a prime candidate for a deep mycotic infection was present in
this report. Evidence existed for the source of the infection being the con¬ taminated soil to which the patient had been exposed. Primary pulmo¬ nary system involvement was sub¬ stantiated by positive cultures that were obtained from bronchial wash¬ ings. The laryngeal disease could have arisen from a hematogenous or a direct implantation route. The prob¬ able reason why the blood gases did not return to normal values after tra¬ cheostomy is because of the left mainstem bronchial edema, most likely due to the inflammatory reaction that affected the entire tracheobronchial tree and larynx. The paucity of radiographic findings in the chest x-ray film in the presence of extensive dis¬ ease has been previously observed in numerous reports of pulmonary cryp¬ tococcosis.
Pseudoepitheliomatous hyperplasia
Fig 3.—Biopsy specimen of false vocal cord with characteristic pseudoepitheliomatous hyperplasia prior to treatment. Mucosal surface indicated by arrow (Alcian blue stain, original magnification 100).
tracheobronchial tree, with severe narrow¬ ing of the left mainstem bronchus that was apparently secondary to edema. Results of
biopsy were negative. A pathology report of the biopsy speci¬ men of the right false vocal cord indicated severe pseudoepitheliomatous hyperplasia of the epithelium. Numerous budding yeast cells were surrounded by large cap¬ sules that were positive to staining with Alcian blue. No hyphal forms were seen. Acid-fast stains were negative. The diag¬ nosis was cryptococcosis (Fig 3 and 4). a
Treatment On Dec 12, 1973, intravenous therapy with amphotericin was initiated, and the patient received a total dose of 2 gm over a 30-day period. Progressive improvement in the airway obstruction enabled us to decannulate three weeks after initiation of
chemotherapy. On May 27, 1973, the patient was read¬ mitted to the University Hospital, where direct laryngoscopy and biopsy were per¬ formed. Mild edema of the false vocal cords persisted. Histopathologic examina-
of the mucosal epithelium has been described in association with neo¬ plasia, ie, granular cell myoblastoma, early malignant neoplasm and in blastomycosis.9 This has been re¬ ported as rarely occurring in mucocutaneous Cryptococcus infection.10 These mucosal changes were not pres¬ ent at the time of the post-treatment biopsy, which may indicate some di¬ rect relationship to the presence of the organism inciting this reaction in epithelial cells. An overlooked positive sputum cul¬ ture containing C neoformans was found in the patient's chart, dated two years prior to his present admis¬ sion to the hospital. There have been rare reported cases of patients sur¬ viving this length of time with un¬ treated C neoformans infections. Laryngograms taken prior to initi¬ ation of chemotherapy were not help¬ ful in making a specific diagnosis, but did reveal the extensive nature of the laryngeal disease.
Downloaded From: http://archotol.jamanetwork.com/ by a University of British Columbia Library User on 06/17/2015
Fig 4.—Numerous encapsulated cryptococcal organisms in false vocal cord submucosa. Several cian blue stain, original magnification 400). In all cases of cryptococcosis, a spi¬ nal puncture should be performed, with appropriate studies done to eliminate the possibility of central nervous system involvement. India ink preparations will give reliable in¬ formation regarding the presence of the organism. is presently the Amphotericin drug of choice for cryptococcal infec-
tions. While our patient had an excel¬ lent response to amphotericin B, the toxic side-effects may cause substan¬ tial morbidity. A recent report of na¬ sal C neoformans treatment with flucytosine (Ancobon), a new antifungal agent, shows promise due to its decreased renal toxicity."' In retro¬ spect, this would have been the pre¬ ferred drug because of the pre-
budding
existing
present in
forms indicated
renal
disease
by arrow (Al¬
that
was
patient. Briggs et al found cryptococcal se¬ rum antigen levels to be helpful in diagnosing and following the pa¬ our
tient's response to treatment.5 Name and Trademark of Drug
Nonproprietary
Amphotericin B—Fungizone.
References 1. Emmons C (ed): Medical Mycology. Philadelphia, Lea & Febiger Publishers, 1970, pp 186\x=req-\
206. 2. Gill W: Torula mycosis in man: Upper respiratory tract. Ann Otol Rhinol Laryngol 44:1140-1150, 1935. 3. Lyons G: Mycotic disease of the human larynx. Ann Otol Rhinol Laryngol 79:162-175,1966. 4. Haugen R, Baker R: Pulmonary lesions of cryptococcosis. Am J Clin Pathol 24:1381-1390,
1954. 5. Briggs DR, Barney PL, Bahu RM: Nasal cryptococcosis. Arch Otolaryngol 100:390-392, 1974. 6. Wolstenholme GEW: Systemic Mycosis. Ciba Symposium. Boston, Little Brown & Co, 1968, pp 26-36. 7. Littmann ML, Zimmerman LE: Cryptococcosis. New York, Grune & Stratton Inc, 1956, p 50.
8. Warr W, Bates J: The spectrum of pulmonary cryptococcosis. Ann Int Med 69:1109-1116, 1968. 9. Robbins SL: Pathological Basis of Disease. Philadelphia, WB Saunders Co, 1974, p 1408. 10. Schwarz J: in Paparella M and Shumrich D (eds): Otolaryngology: Philadelphia, WB Saunders Co, 1973, chap 15, p 447.
Downloaded From: http://archotol.jamanetwork.com/ by a University of British Columbia Library User on 06/17/2015
Reese, MD, Joe B. Colclasure,
of the MD
\s=b\ An unusual case of cryptococcosis of the larynx initially developed as an acute upper airway obstruction that necessitated tracheostomy. Concomitant findings were tracheobronchial ulcerations and edema with severe mainstem bronchial constriction on the left side. Budding "yeast-like organisms" that were consistent with Cryptococcus neoformans appeared in tissue specimens. Epithelial changes that were consistent with pseudoepitheliomatous hyperplasia occurred in areas in the immediate vicinity of the organisms. Sputum and bronchial washing cultures grew nonmycelial, mucinous, encapsulated forms that were positive to staining with mucicarmine and Alcian blue. Treatment with amphotericin B resulted in resolution of the laryngeal obstruction, permitting decannulation. Follow-up direct laryngoscopy and biopsy three months after completion of therapy revealed only mild edema of the false vocal folds. No organisms were found in the tissue, and the pseudoepitheliomatous hyperplastic mucosal changes had resolved.
(Arch Otolaryngol 101:698-701, 1975)
the past, microbiologists have been inconsistent about termi¬ nology and specific identification of the Cryptococcus neoformans orga¬ nism with respect to deep mycotic in-
In
Accepted
publication June 26, 1975. Department of Otolaryngology, University Hospital, Little Rock, Ark. Reprint requests to 1110 W Elm, Rogers, AR 72756 (Dr Reese). From the
for
Larynx
fections. For some time, the term "Torula" was inappropriately used to describe cryptococcosis. European blastomycosis and Busse-Buschke dis¬ ease are two of the various names for C neoformans infections.1 One refer¬ ence prior to 1940 considered Monilia, North American blastomycosis, and cryptococcosis to be members of the blastomycosis group. These factors lend confusion to interpretation of the earlier reports of laryngeal mycoses. A review of the literature reveals
several reports of suspected mycotic diseases of the larynx, but none could be found specifically incriminating C
neoformans.'2·3 Close scrutiny of proved cases of upper respiratory cryptococcosis re¬ veals that the disease is primarily pulmonary, with secondary involve¬ ment of other structures.4 Extra¬ is most com¬
pulmonary involvement
in the central nervous system, but involvement of the prostate, mon
spleen, liver, kidney, nasopharynx, paranasal sinuses, and nasal and oral lesions have also been reported.4-5 Cryptococcus neoformans infections
from inhalation of the orga¬ nisms that are found in pigeon and other avian solid excrements and soil. Infections caused by this organism have been thought to be present as an opportunist in patients with debili¬ tating systemic disease and in per¬ sons taking steroids or cytotoxic sub¬ stances." The disease in humans is not occur
contagious.
In a review of 220 cases of infec¬ tions with C neoformans, the central nervous system was involved in 81%, and the pulmonary system in 20%. These statistics indicate the transi¬ tory, mild, and frequently unrecog¬ nized nature of the pulmonary dis¬ ease. Hematogenous spread to other sites occurs mainly to the central ner¬ vous system. The frequent transitory nature of the pulmonary involvement is further elucidated by the fact that many proved cases of C neoformans of the lung are known to have healed spontaneously, leaving only the dis¬ seminated disease persisting. The pulmonary lesion heals by encapsula¬ tion, with no residual scar.1 With pulmonary involvement, the diagnosis is most commonly estab¬ lished by sputum exam. With extra¬ pulmonary disease, the diagnosis is made by identifying the organisms in the tissue. Cutaneous and mucous membrane involvement usually is a manifestation of disseminated infec¬ tion. Histopathologic differentiation is sometimes difficult, and the tissue form of C neoformans is frequently confused with Blastomyces dermatitidis. The mucopolysaccharide capsule is thick, and elicits a mild cellular re¬ action in tissue. This capsule charac¬ teristically stains with mucicarmine.7 Definitive identification of C neo¬ formans by culture must be made by the following criteria: (1) the orga-
Downloaded From: http://archotol.jamanetwork.com/ by a University of British Columbia Library User on 06/17/2015
Fig 2—Contrast laryngogram with edema of true and false vocal cords.
Fig 1 —Chest x-ray film disease.
on
admission. Paucity of
nism grows in mucoid colonies on the Sabouraud agar medium at 37 C; (2) culture grows encapsulated, nonmycelial yeast forms; (3) inability to fer¬ ment sugars; and (4) positive reaction
production tests.8 Complement fixation and direct fluorescent antibody tests have been to urease
unreliable. Our case is reported to describe the first known involvement of the larynx by C neoformans with resultant chronic airway obstruction and a sub¬ sequent acute respiratory emergency that required tracheostomy. REPORT OF A CASE A 47-year-old man was admitted to the University Hospital emergency room on Nov 29, 1973, with the chief complaint of gradual onset of hoarseness and dyspnea of two years' duration. On the day of ad¬ mission he had developed severe respira¬ tory distress that required tracheostomy. Within the previous two years prior to the onset of symptoms he had worked in
soil that had been treated with chicken ma¬ nure. During prior admissions to this hos¬ pital in 1970, diagnoses of exogenous obe¬ sity, hypertension of renal origin, chronic proteinuria, and arteriosclerotic heart dis¬ ease had been identified and evaluated by the Medicine Department. Classification of the organic heart disease was (1) arterio¬ sclerotic heart disease, (2) cardiomegaly, (3) probably congestive heart failure, and
(4)
radiographie
not
chronic
evidence of
pulmonary
drug-induced. The cause of proteinuria was not known.
his
Laboratory Findings Laboratory studies disclosed the follow¬ ing values: hemoglobin, 13.8 gm/100 ml; hematocrit, 39%; white blood cell (WBC) count, 5,800/cu mm with 70% neutrophils, 6% eosinophils, 10% lymphocytes, and 12% monocytes; platelet count, 251,000/cu mm; blood urea nitrogen, 57 mg/100 ml; serum creatinine, 4.7 mg/100 ml; and serum alka¬ line phosphatase, 58 King-Armstrong units/ 100 ml. The levels of serum electrolytes, se¬ rum glutamic oxaloacetic transaminase, serum bilirubin, serum cholesterol, and se¬ rum triglycérides were normal. The 24hour urine protein level was 46 gm, urine creatinine clearance was 88 ml/min, the se¬ protein level was 6.2 gm/100 ml, and the serum albumin level was 2.9 gm/100 ml. The latter values were determined on his previous admission. The direct fluores¬ cent antibody tube agglutination and latex agglutination tests for Crytococcus were rum
negative.
The blood gas values
prior
to tracheos¬
tomy were as follows: arterial oxygen pres¬
sure, 38 mm Hg; arterial carbon dioxide pressure, 32 mm Hg; pH, 7.490; H% 32; and HCO5, 23. The blood gas values after tra¬ cheostomy were as follows: arterial oxygen pressure, 60 mm Hg; arterial carbon diox¬ ide pressure, 35 mm Hg; pH, 7.410; H*, 38;
and
HCO3, 21.
Physical Examination Physical examination revealed
the fol-
lowing: blood pressure, 155/100 mm Hg; pulse rate was 84 beats per minute; respi¬ rations, 36/min; and rectal temperature, 36.7 C (98 F). Apparent signs and symp¬ toms of upper airway obstruction were present, along with expiratory and inspira¬ tory wheezes by auscultation of both lungs. Pitting edema (4 + ) of both feet was noted.
Radiographic Examination Chest x-ray film revealed cardiomegaly with left ventricular prominence, and a prominent right hilum. No infiltrates were seen (Fig 1). Tomograms of the right hilum revealed that no cavity was pres¬ ent. Sinus x-ray films and intravenous pyelograms were negative. A laryngogram revealed laryngeal edema involving epi¬ glottis and false and true vocal cords, with decreased mobility of the true vocal cords. There was asymmetry of the subglot¬ tic arches (Fig 2).
Additional
Findings
A spinal tap was performed on Nov 29, 1973. No WBCs or red blood cells were present. A VDRL test for syphilis was negative. An India ink preparation was negative, and a culture was negative for
growth.
Transnasal fiberoptic bronchoscopy re¬ vealed multiple punctate ulcers with white exudates involving the entire tracheobron¬ chial tree. Bronchial washings cultured C
neoformans.
Direct laryngoscopy and biopsy revealed marked laryngeal edema and glottic ob¬ struction, and multiple, white, raised exudative lesions of the mucosa. A biopsy specimen of the right false vocal cord was positive for a "yeast-like" organism con¬ sistent with C neoformans. On Nov 30, 1973, transtracheal fiberoptic bronchoscopy revealed scattered white plaques on the mucosa of the entire
Downloaded From: http://archotol.jamanetwork.com/ by a University of British Columbia Library User on 06/17/2015
tion failed to reveal any organisms in the tissue, and there was complete resolution of the pseudoepitheliomatous hyperplasia. The patient was last seen on March 16, 1975, in good health, with continuing im¬ provement in the quality of his voice.
COMMENT
The classic example of a debilitated patient being a prime candidate for a deep mycotic infection was present in
this report. Evidence existed for the source of the infection being the con¬ taminated soil to which the patient had been exposed. Primary pulmo¬ nary system involvement was sub¬ stantiated by positive cultures that were obtained from bronchial wash¬ ings. The laryngeal disease could have arisen from a hematogenous or a direct implantation route. The prob¬ able reason why the blood gases did not return to normal values after tra¬ cheostomy is because of the left mainstem bronchial edema, most likely due to the inflammatory reaction that affected the entire tracheobronchial tree and larynx. The paucity of radiographic findings in the chest x-ray film in the presence of extensive dis¬ ease has been previously observed in numerous reports of pulmonary cryp¬ tococcosis.
Pseudoepitheliomatous hyperplasia
Fig 3.—Biopsy specimen of false vocal cord with characteristic pseudoepitheliomatous hyperplasia prior to treatment. Mucosal surface indicated by arrow (Alcian blue stain, original magnification 100).
tracheobronchial tree, with severe narrow¬ ing of the left mainstem bronchus that was apparently secondary to edema. Results of
biopsy were negative. A pathology report of the biopsy speci¬ men of the right false vocal cord indicated severe pseudoepitheliomatous hyperplasia of the epithelium. Numerous budding yeast cells were surrounded by large cap¬ sules that were positive to staining with Alcian blue. No hyphal forms were seen. Acid-fast stains were negative. The diag¬ nosis was cryptococcosis (Fig 3 and 4). a
Treatment On Dec 12, 1973, intravenous therapy with amphotericin was initiated, and the patient received a total dose of 2 gm over a 30-day period. Progressive improvement in the airway obstruction enabled us to decannulate three weeks after initiation of
chemotherapy. On May 27, 1973, the patient was read¬ mitted to the University Hospital, where direct laryngoscopy and biopsy were per¬ formed. Mild edema of the false vocal cords persisted. Histopathologic examina-
of the mucosal epithelium has been described in association with neo¬ plasia, ie, granular cell myoblastoma, early malignant neoplasm and in blastomycosis.9 This has been re¬ ported as rarely occurring in mucocutaneous Cryptococcus infection.10 These mucosal changes were not pres¬ ent at the time of the post-treatment biopsy, which may indicate some di¬ rect relationship to the presence of the organism inciting this reaction in epithelial cells. An overlooked positive sputum cul¬ ture containing C neoformans was found in the patient's chart, dated two years prior to his present admis¬ sion to the hospital. There have been rare reported cases of patients sur¬ viving this length of time with un¬ treated C neoformans infections. Laryngograms taken prior to initi¬ ation of chemotherapy were not help¬ ful in making a specific diagnosis, but did reveal the extensive nature of the laryngeal disease.
Downloaded From: http://archotol.jamanetwork.com/ by a University of British Columbia Library User on 06/17/2015
Fig 4.—Numerous encapsulated cryptococcal organisms in false vocal cord submucosa. Several cian blue stain, original magnification 400). In all cases of cryptococcosis, a spi¬ nal puncture should be performed, with appropriate studies done to eliminate the possibility of central nervous system involvement. India ink preparations will give reliable in¬ formation regarding the presence of the organism. is presently the Amphotericin drug of choice for cryptococcal infec-
tions. While our patient had an excel¬ lent response to amphotericin B, the toxic side-effects may cause substan¬ tial morbidity. A recent report of na¬ sal C neoformans treatment with flucytosine (Ancobon), a new antifungal agent, shows promise due to its decreased renal toxicity."' In retro¬ spect, this would have been the pre¬ ferred drug because of the pre-
budding
existing
present in
forms indicated
renal
disease
by arrow (Al¬
that
was
patient. Briggs et al found cryptococcal se¬ rum antigen levels to be helpful in diagnosing and following the pa¬ our
tient's response to treatment.5 Name and Trademark of Drug
Nonproprietary
Amphotericin B—Fungizone.
References 1. Emmons C (ed): Medical Mycology. Philadelphia, Lea & Febiger Publishers, 1970, pp 186\x=req-\
206. 2. Gill W: Torula mycosis in man: Upper respiratory tract. Ann Otol Rhinol Laryngol 44:1140-1150, 1935. 3. Lyons G: Mycotic disease of the human larynx. Ann Otol Rhinol Laryngol 79:162-175,1966. 4. Haugen R, Baker R: Pulmonary lesions of cryptococcosis. Am J Clin Pathol 24:1381-1390,
1954. 5. Briggs DR, Barney PL, Bahu RM: Nasal cryptococcosis. Arch Otolaryngol 100:390-392, 1974. 6. Wolstenholme GEW: Systemic Mycosis. Ciba Symposium. Boston, Little Brown & Co, 1968, pp 26-36. 7. Littmann ML, Zimmerman LE: Cryptococcosis. New York, Grune & Stratton Inc, 1956, p 50.
8. Warr W, Bates J: The spectrum of pulmonary cryptococcosis. Ann Int Med 69:1109-1116, 1968. 9. Robbins SL: Pathological Basis of Disease. Philadelphia, WB Saunders Co, 1974, p 1408. 10. Schwarz J: in Paparella M and Shumrich D (eds): Otolaryngology: Philadelphia, WB Saunders Co, 1973, chap 15, p 447.
Downloaded From: http://archotol.jamanetwork.com/ by a University of British Columbia Library User on 06/17/2015
