Pulmonary Disease Caused by Candida Species

HENRY MASUR, M.D. P. PETER ROSEN, M.D. DONALD ARMSTRONG,

M.D.

New York, New York

Candida species are often found in sputum specimens. Their role as a possible cause of pulmonary disease is a frequent consideration, particularly in patients receiving immunosuppressive or longstanding antimicrobial therapy. At Memorial Hospital and New York Hospital, 30 patients with histologic evidence of Candida pulmonary infection were identified over a two year period. These infections reached the lungs by hematogenous spread in 10 patients and by aspiration in 16 patients. Most of the patients had malignant neoplastic disease. The Candida pulmonary disease appeared to be a significant clinical factor in only three cases. Experience from our institutions and from the literature indicates that Candida species rarely cause significant pulmonary disease. When such involvement is extensive, the patient is usually terminally ill from multiple other factors. Candida species are found in from 3 to 84 per cent of sputum specimens depending on the population surveyed and the methods used for isolation [l-4]. The significance of these organisms in the sputum is uncertain [l-3], particularly in patients receiving immunosuppressive agents, in whom invasive Candida infections do occur in many areas of the body. Although descriptions of Candida pneumonia are available in standard texts, we have been impressed by the rarity of histologic evidence for pulmonary involvement in our patient population, and the paucity of definitive cases in the English literature [ 1,3,4-61. This study was undertaken to determine the frequency of pulmonary lesions due to Candida species (hereafter referred to as Candida), and to define the clinical and pathologic features of these lesions at Memorial Sloan-Kettering Cancer Center and at New York Hospital, over a two year period. METHODS

From the Infectious Disease Service, Department of Medicine and the Department of Pathology, Memorial Sloan-Kettering Cancer Center, and the Infectious Disease Division, the New York Hospital, New York, New York, and Cornell University Medical College, New York, New York. Requests for reprints should be addressed to Dr. Donald Armstrong, Memorial Hospital, 1275 York Avenue, New York, New York 10021. Manuscript accepted March 30. 1977.

914

December 1977

All autopsy protocols for 1973 and 1974 at Memorial Sloan-Kettering Cancer Center were reviewed (965 cases). For purposes of comparison, all autopsy protocols for the identical period at the New York Hospital were reviewed (995 cases). In addition, records of all lung biopsies performed at these institutions from 1971 to 1975 were reviewed. We reviewed all pathology slides, the clinical chart and the chest roentgenogram for each patient in whom a diagnosis of Candida pulmonary infection was made, or in whom a fungus morphologically consistent with Candida was seen histologically in the lungs or pleura. Patients were included in this series only if we identified Candida histologically, and parenchymal invasion was present. Only one patient had biopsy proved Candida pulmonary infection. She subsequently died and underwent autopsy elsewhere; she is discussed separately.

The American Journal of Medicine

Volume 63

PULMONARY

Candida organisms were identified histologically on the basis of typical morphologic features in sections stained with hematoxylin and eosin, periodic acid-Schiff or methenamine silver. Typically, the yeast forms were round or oval, 2.5 to 6 mm in diameter, and occurred singly, in clusters or in chains. Pseudohyphae were typically elongated blastospores which were adherent to neighboring blastospores, producing chains. The method of Silva-Hutner [7] was used to classify Candida species isolated in the microbiology laboratory. An attempt was made to identify the route by which Candida spread to the lungs by studying the distribution of the organisms, and their relationship to blood vessels and air passages. Since this study was retrospective, the pathologic material was limited to that selected by the prosector. In four of 30 cases, the route could not be ascertained with certainty. In the others, there appeared to be sufficient evidence to distinguish hematogenous from bronchial spread to the lungs. The criteria used were those commonly employed in evaluating autopsy material which had been used in a prior study of candidiasis [56]. Hematogenous dissemination was thought to be present when there was no evidence of bronchial spread (as described herein), and Candida pseudohyphae were found growing from within pulmonary vessels into surrounding lung parenchyma (Figure 1). In cases judged to fit this pattern, there was deeply invasive infection of another organ system, often the gastrointestinal tract, that appeared to be the source of dissemination into the blood stream. Bronchial spread was evidenced by intrabronchial and alveolar changes associated with aspiration in most cases. Within bronchi it was possible to identify aspirated oropharyngeal contents including squamous cells, mucus, food particles and the fungal organisms. In instances included under this category, this material lay free within the lumen, and there was fungal invasion of the bronchial mucosa or wall. Presence of similar material within the alveoli, sometimes accompanied by detached respiratory epithelium, was further evidence of aspiration; alveolar lesions frequently featured hemorrhage and a variable inflammatory reaction in the surrounding tissue.

DISEASE CAUSED BY CANDIDA

SPECIES---MASIJR

ET AL.

In this retrospective analysis, a systematic quantitation of pulmonary involvement could not be devised using the available information. Therefore, pulmonary involvement by Candida was judged as “significant,” “contributory” or “insignificant” on the basis of quantity of Candida seen, amount of lung tissue involved and the extent of other factors that might have compromised pulmonary function, such as tumor, hemorrhage, aspirated material or other infectious processes. Involvement was considered to be significant if sufficient pulmonary parenchyma was invaded by C#andida to have potential clinical significance, and if the amount of tissue invaded by Candida was considerably grealer than that involved by hemorrhage, neoplastic disease, chemical aspiration pneumonitis or other factors. In each case judged to be significant, more than 75 per cent of at least two lobes was involved by numerous foci of Candida. Involvement was considered to be contributory if sufficient pulmonary parenchyma was invaded by Candida to have potential clinical significance, but other factors, such as hemorrhage, neoplastic disease or chemical aspiration pneumonitis, also involved extensive pulmonary parenchyma. Involvement was considered to be insignificant if only a few microscopic foci of Candida were found. In each case described as insignificant in this series, fewer than 4 microscopic foci were found. Twelve patients in whom there was no inflamlmatory response to Candida were included in this series, since each of these patients was severely granulocytopenic, and other organs showed no histopathologic evidence of postmortem growth. RESULTS There were 30 patients with pulmonary Candida infection (Tables I through Ill). Twenty-five, all with underlying neoplastic disease, were from Memorial Hospital (2.6 per cent of autopsies); five, three with underlying neoplasm, were from New York Hospital (0.5 per cent of autopsies). There were three significant, one contributory and 12 insignificant pulmonary Candida

Low magnification view of 1. Candida pseudohyphae growing from a

Figure

thrombosed blood vessel lumen and radiating into adjacent lung parenchyma. Gomori’s methenamine silver stain.

December

1977

The American

Journal

of Medicine

Volume 63

915

Embryonal rhabdomyosarcoma __ -.

3

Acute lymphocytic leukemia

Acute myelogenous leukemia None documented

5

6

8

Pyelonephri tis

Underlying 0 isease

Case No.

7

II

TABLE

ND

_

ND

_

Bilateral infiltrates for 3 weeks

Clinical Pulmonary Problems

Postoperative infiltrates

Bilateral infiltrates for 9 weeks

None

.~-

+

-

_

-

+

Oral Candidiasis _ _~~.

Pulmonary

None until terminal aspiration

Bilateral pulmonary infiltrates for 4 weeks Unilateral infiltrate for 4 days

Candida i._~~____..___

Sputum Culture _______

-

_

_

Infection

Hematogenous

Aspiration

_

Hematogenous

Hematogenous

Route of Entry of Candida into Lungs -~

-.__

Aspiration

Aspiration

Aspiration

Route of Entry of Candida into Lungs ___.-

+

+

+

Postmortem Esophageal Candidiasis .___.-__

Infection

+

-

+

PostOral mortem Candi- Esophageal diasis Candidiasis _~ ___~.._

Pulmonary

Clinical Pulmonary Problem

Candida -____

Sputum Culture

Contributory

Hodgkin’s disease

Acute lymphocvtic leukemia

2

1

Underlying 0 isease

Case No.

Significant

I

TABLE

Throughout bronchial

All lobes

All lobes

All lobes

Extent of Pulmonary Involvement __-.

Both lower lobes

Both lower lobes

All lobes

Extent of Pulmonary Involvement

Lung Culture

Candida tropicalis

Other Organs Involved by Candida

Entire gastrointestinal tract, liver, kidney, brain

Brain, liver, spleen, bladder

Comments

Cause of Death

Respiratory failure

Seotic shock

Septic shock, diffuse hemorrhage

Candida endocarditis with Candida abscesses associated with consolidation of all lobes, but acute and chronic hemorrhage the predominant pulmonary lesion Extensive pulmonary hemorrhage; primary site of Candida invasion probably the bladder Atypical mycobacterium more extensive than the numerous Candida abcesses; primary site of Candida invasion probably the gastrointestinal tract Extensive Candida abscesses of bronchial tree without siqnificant paren-

Comments

Numerous small Candida abscesses superimposed on acute and organizing bronchopneumonia and massive pulmonary hemorrhage; minimal aspiration of vegetable particles Extensive aspirated material throughout bronchi; diffuse pulmonary hemorrhage and necrotic foci in lower lobes surrounding foci of Candida Extensive aspiration of blood, mucous and Candida, superimposed on patchy hemorrhage

Disseminated candidiasis

Bacterial sepsis, aspiration pneumonia

Renal failure, gastrointestinal hemorrhage, septic shock, respiratory insufficiency Renal failure, hepatic failure, respiratory failure

Cause of Death

Ventricular endocardium, pericardium peritoneum kidney, spleen

Esophagus

None

Esophagus, stomach

Other Organs Involved by Candida

Candida, not albicans

-

-

-

Lung Culture

NOTE,

TABLE

4

Solid

AML

-

xute

Ttlmor

myelogenous

3

Lymptlornd

leukemia;

12 ND)

7

AML

ALL

None

= acure

aspiration

Termin,il

>

>

lymphw_ytli

No.

infection

,1 week

infiltrates

ALL

G

Bilateral

tumor

2

Sohd

None

1 week InfIltrate

Unilateral

1 week

inflltrates

Bilateral

Clinical Pulmonary Problem

Pulmonary

1

3

I

AML

Lymphoma

3

2

ALL

1’2 ND)

(No.1

Positive Sputum Culture for Candida

Candida

No.

Insignificant

Underlying Disease

III

1

Involved

Esophagus t

1

leukemia;

Asperg~llus

hemorrhage

Extensive

aspiration

Extensive

ND

no,

Only

kidney

Esophagus

stomach

Esophdgus

only

Esophagus

Esophagus

Oral

tlete~:iuneil

3

6

a

and

and

Aspiration Portal of Entry (12 patients)

1

2

thdn

only

3 nrgans

hlote

Oral

(7 patients)

Nonpulmonary Candidiasis

of Entry

1

3

Mucor

Portal

No.

Aspergillus

Tumor

aspiration

Extenstve

hemorrhage

Extensive

Hematogenous

Significant Pulmonary Pathology

1

2

4

2

5

7

2

No.

not

troplcalls

krusel

Negative

C

C.

C

C. albicatv

culture

nlblcans

culture

:I oplcdl?

Negative

c

C. albicans

Lung Culture

shock

4

3

Septic

shock

hernlatlon

Uncal

Enciocn~n-l~tis

Hemorrhaqe

pneumonld

BacterIaI 1

Aspiration 1

Pneumon,:i

Septic

candtcliasis

Disseminated

Cause of Death

3

0

6

No.

1

1

1

2

2

5

1

4

PULMONARY

DISEASE

CAUSED

BY CANDIDA

SPECIES-MASUR

ET AL.

infections related to aspiration. There were no significant, three contributory, and seven insignificant pulmonary Candida infections related to hematogenous spread. Among the four patients in whom the portal of entry could not be determined, there were one contributory and three insignificant Candida pulmonary infections. Pulmonary Involvement in Patients with Neoplastic Disease. The majority of the patients (22 of 23) in this group had leukemia or lymphoma, and 24 of 28 patients had had granulocytopenia (

Pulmonary disease caused by Candida species.

Pulmonary Disease Caused by Candida Species HENRY MASUR, M.D. P. PETER ROSEN, M.D. DONALD ARMSTRONG, M.D. New York, New York Candida species are o...
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