DOI:10.2214/AJR.07.2389
AJR 2007; 189:1397-1401
© American Roentgen Ray Society
Necrotizing Granuloma of the Lung: Imaging Characteristics and Imaging-Guided Diagnosis
Rennae Thiessen1,
Jean M. Seely1,
Frederick R. K. Matzinger1,
Prachi Agarwal1,2,
Karen L. Burns3,
Carole J. Dennie1 and
Rebecca Peterson1
1 Department of Diagnostic Imaging, The Ottawa Hospital, 1053 Carling Ave.,
Ottawa, ON K1Y 4E9, Canada.
2 Present address: Department of Radiology, University of Michigan Medical
Center, Ann Arbor, MI.
3 Department of Pathology, The Ottawa Hospital, Ottawa, ON, Canada.
Received April 9, 2007;
accepted after revision June 24, 2007.
Address correspondence to J. M. Seely
(jeseely{at}ottawahospital.on.ca).
Abstract
OBJECTIVE. The purpose of this study was to assess CT findings and
the sensitivities of imaging-guided fine-needle aspiration (FNA) biopsy and
core needle biopsy in the diagnosis of necrotizing granuloma of the lung.
CONCLUSIONS. The CT characteristics of necrotizing granuloma are
indistinguishable from those of malignant tumors; tissue diagnosis therefore
is necessary. Core needle biopsy is a sensitive method for diagnosing
necrotizing granuloma of the lung, but FNA biopsy is insufficient for
diagnosis.
Keywords: CT-guided biopsy • lung biopsy • necrotizing granuloma • pulmonary nodule • solitary pulmonary nodule
Introduction
Assessment of a solitary pulmonary nodule is a common challenge for chest
radiologists. Despite the existence of advanced imaging techniques, it may
still be impossible to differentiate benign from malignant focal lung lesions.
This problem is magnified by the increasing number of incidental or
screening-detected lung nodules and the medicolegal implications of missing a
case of lung cancer [1]. At
many North American medical centers, suspicious pulmonary nodules are resected
at thoracotomy without preoperative diagnosis. At others, preoperative FDG
PET/CT confirmation of a metabolically active lung lesion leads to lung
resection for diagnosis [2]. In
areas where granulomatous lung infections are endemic, however, false-positive
PET results, in which PET shows markedly increased uptake of FDG suggesting
cancer but the pathologic finding is benign, can lead to unnecessary
thoracotomy [3]. Transthoracic
needle biopsy (TTNB) has been proved accurate in the evaluation of focal lung
lesions. Although it has been highly sensitive (70–100%) in the
diagnosis of intrathoracic malignant tumors in many studies
[4,
5], fine-needle aspiration
(FNA) biopsy (22- to 25-gauge needle) has recognized limitations in obtaining
a specific benign diagnosis
[6]. Therefore, when a benign
entity is suspected, core needle biopsy is the optimal TTNB technique for
achieving a specific diagnosis
[4].
In the Saint Lawrence River valley, as in several other similar North
American valley regions, there is a high prevalence of endemic fungi,
predominantly those that cause histoplasmosis and blastomycosis. Infection can
result in focal lung lesions that mimic lung cancer
[7]. To minimize the rate of
lung resection for benign disease, all patients with solitary indeterminate
lung lesions undergo preoperative assessment with needle biopsy. Our practice
has encountered a considerable number of necrotizing granulomas diagnosed at
imaging-guided TTNB of lung lesions. To our knowledge, the imaging features of
these lesions have not been previously described. We undertook this study to
determine the clinical and imaging features of histopathologically proven
necrotizing granuloma. Our second objective was to determine the optimal
method of obtaining the diagnosis of necrotizing granuloma by comparing the
sensitivities of FNA biopsy and core needle biopsy.
Materials and Methods
We performed a retrospective review of the pathology database of our
institution to find patients who received the diagnosis of necrotizing
granuloma in the period 1997–2004. Hospital and referring physicians'
records were reviewed for prebiopsy clinical features, investigations
performed, biopsy technique, and clinical and imaging follow-up. Clinical
characteristics evaluated included age, sex, smoking status, history of
malignant disease, and intervals of follow-up. Results of bronchoscopy, lung
resection, and microbiologic stains and cultures were recorded. Imaging
characteristics were evaluated in the cases of patients with pathologically
proven necrotizing granuloma and chest CT scans available for review. Images
were independently assessed by two independent observers. Discrepancy between
observers was resolved by consensus of two experienced thoracic radiologists.
Imaging features recorded included lesion size, location, margins, and
distance from the pleura and the presence of calcification or cavitation,
associated pleural thickening, emphysema, or lymphadenopathy. All patients
with a primary diagnosis of necrotizing granuloma were included in the
determination of the sensitivity of imaging-guided biopsy.
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Fig. 1B —74-year-old woman with necrotizing granuloma proven with
imaging-guided core needle biopsy. Axial CT scan at same level as A
obtained at mediastinal setting shows homogeneous soft-tissue attenuation of
lesion.
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Fig. 2A —36-year-old woman with necrotizing granuloma of lung proven
with core needle biopsy. Axial CT scan shows lobulated 3.4-cm mass in left
lower lobe with surrounding ground-glass attenuation.
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Fig. 2B —36-year-old woman with necrotizing granuloma of lung proven
with core needle biopsy. Axial CT at same level as A obtained in
mediastinal window setting shows mass of homogeneous soft-tissue attenuation
contiguous to left hilar adenopathy.
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Fig. 2D —36-year-old woman with necrotizing granuloma of lung proven
with core needle biopsy. Photomicrograph of histologic section of specimen at
higher magnification shows interface of necrosis (arrows) with rim of
histiocytes and scattered lymphocytes (arrowheads) in characteristic
appearance of necrotizing granuloma. (H and E, x4)
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FNA was performed with a 22- or 25-gauge needle. One to three aspirates
were obtained, with a median of two. If the first two aspirates are acellular
or nondiagnostic, it is unlikely that subsequent samples would be helpful, and
cytologic architecture is often required. Therefore, we typically proceeded
with core needle biopsy. Core needle biopsy was performed with a 20-gauge
needle by a coaxial technique through a 19-gauge introducer needle with an
automated biopsy gun (Mannan, Medical Device Technologies). A range of two to
10 and a median of seven cores were obtained to maximize the diagnostic yield.
A cytotechnologist was present for all lung biopsies performed after July
2002. FNA biopsy and core needle biopsy were performed by the same thoracic
radiologists, all with more than 10 years of experience in thoracic
radiology.
Results
A total of 76 patients had a pathologic diagnosis of necrotizing granuloma.
Twenty-five of these patients were excluded because another diagnosis was
later confirmed, including nine additional malignant pulmonary tumors, five
sarcoid tumors, and one healed granuloma. In the patients with malignant
disease, the diagnosis of necrotizing granuloma was an incidental finding;
that is, there were no false-positive results in the study group. Three
patients were excluded because no discrete nodule was apparent, and seven were
excluded because of discordance between the patient's name and the hospital
medical record number. Among the 51 remaining patients, 43 (28 women, 15 men)
had chest CT scans available for review. The mean patient age was 59 years
(median, 61 years; range, 23–81 years). Most of the patients had a
smoking history (29 smokers vs 12 nonsmokers), and eight had a history of
malignant disease.
Imaging Features
All 43 of the patients with available chest CT scans underwent TTNB. The CT
scans were obtained in 2.5- and 5-mm-thick slices, some with and others
without contrast enhancement, which was not recorded in our study. Dynamic
contrast enhancement of the lesions was not determined. The size of lesions
ranged from 0.5 to 7.0 cm in diameter. Five lesions measured 1 cm or less; 25,
1.1–2.0 cm; and 13, 2.0 cm or more. Margins were spiculated in 19 (Fig.
1A,
1B), lobulated in eight (Fig.
2A,
2B,
2C,
2D), and smooth in 16 cases.
Sixteen patients had additional lesions in the same lobe and 22 patients, in
other lobes. Eight lesions were cavitated (Fig.
3A,
3B), and none had benign
calcification (Fig. 4A,
4B). Mediastinal
lymphadenopathy was present in seven patients and hilar lymphadenopathy (Fig.
2A,
2B,
2C,
2D), in five patients. Most
lesions were peripheral, 84% abutting or within 1 cm of the pleura
(Table 1).
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Fig. 3B —58-year-old woman with necrotizing granuloma proven with core
needle biopsy. Axial CT scan at same level as A in mediastinal window
setting shows cavity has variable wall thickness. There is no associated
calcification.
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Fig. 4A —80-year-old man with necrotizing granuloma diagnosed with
core needle biopsy. Axial CT scan shows lobulated 2.4-cm lesion with adjacent
cylindric bronchiectasis and emphysema in right lower lobe.
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Fig. 4B —80-year-old man with necrotizing granuloma diagnosed with
core needle biopsy. Axial CT scan at same level as A obtained in
mediastinal window setting shows multiple eccentric unusual calcifications in
lesion, none of which is characteristically benign.
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Diagnosis
Diagnosis was achieved with bronchoscopy in one patient, FNA biopsy in one
patient, core needle biopsy in 40 patients, and surgery in nine patients among
the total of 51 patients with a pathologic diagnosis of necrotizing granuloma.
FNA biopsy was performed on 46 (90%) of 51 patients, leading to a definitive
diagnosis of necrotizing granuloma in only one case (sensitivity, 2%). Core
needle biopsy was performed on 43 (84%) of 51 patients and was diagnostic in
40 of 44 patients (sensitivity, 91%). One patient had inconclusive results of
an initial core needle biopsy, but a second core needle biopsy was diagnostic.
There were three false-negative results of core needle biopsy, and all
diagnoses later were made with open lung biopsy. Most of the patients
underwent multiple procedures. Forty-three patients underwent both core needle
biopsy and FNA; three patients underwent FNA, core needle biopsy, and open
lung biopsy; and three patients underwent FNA and open lung biopsy. Six
patients needed only one procedure for diagnosis. Three patients underwent
only open lung biopsy, one patient only FNA, one patient only core needle
biopsy, and one patient only endobronchial biopsy. No patient had an initial
pathologic diagnosis of necrotizing granuloma that was later found to be a
malignant tumor.
Pathologic Features
The pathologic features of necrotizing granuloma include aggregates of
macrophages transformed into epithelium-like cells surrounded by a collar of
mononuclear leukocytes, principally lymphocytes and occasional plasma cells,
and a surrounding area of necrosis
[8]. In the case in which the
diagnosis was made with FNA biopsy, the material submitted contained necrotic
debris, epithelioid cells (macrophages), mixed inflammatory cells, and
fibrosis. Similar abundant material in the cell block allowed the pathologist
to make a confident diagnosis of necrotizing granuloma. In two patients who
needed surgical resection for diagnosis, the core needle biopsy pathology
report read "necrotic material, fibrosis, and chronic
inflammation" but did not indicate a specific diagnosis of necrotizing
granuloma. The other false-negative core needle biopsy result was diagnosed as
organizing pneumonia. Fungal and acid-fast stains or cultures were performed
for 39 (76%) of the patients, but stains were positive in only 11 (28%) of the
39 cases. No material sent for culture grew any organisms.
Discussion
Necrotizing granuloma of the lung is a benign entity. Ulbright and
Katzenstein [9] looked at the
clinical and pathologic features of solitary pulmonary granuloma in an effort
to determine the cause and to provide guidelines for histologic diagnosis.
They found that surgically resected pulmonary nodules contain fungal or
acid-fast organisms in 70% of cases. However, Histoplasma organisms
are difficult to identify, particularly in poorly stained preparations in
which organisms are often initially overlooked, even when the preparations are
from surgical specimens, which would presumably have less sampling error than
the smaller sample obtained with core needle biopsy. In our study, only 11
(28%) of the fungal and acid-fast stains had positive results.
Although most necrotizing granulomas have an infectious cause, it is
necessary to exclude noninfectious causes, such as Wegener's granulomatosis,
necrotizing sarcoidosis, idiopathic bronchocentric granulomatosis, hyalinizing
granuloma, and rheumatoid arthritis, which have overlapping histologic
features [8]. Clinical and
imaging correlation is required in each case. In our study, we excluded five
patients with sarcoid and one with a healed granuloma.
The literature on the imaging findings of necrotizing granulomas is
limited. A recent report [10]
described an enhancing rim of benign solitary pulmonary nodules caused by
Coccidioides immitis in an area in which this organism is endemic.
The margins of these lesions were described as irregular or spiculated, as in
our study, although we did not see an enhancing rim in patients to whom
contrast material was administered (Fig.
2B). We saw spiculated and lobulated margins in most (63%) of the
cases and found that these benign lesions were indistinguishable from other
malignant nodules. Although 37% of the lesions were smoothly marginated,
suggesting benignity, all lesions were suspected of being lung cancer,
prompting biopsy. The lesions varied in size from 5 mm to 2 cm or greater,
most (58%) measuring 1–2 cm, and 30% being 2.0 cm or larger. Only five
(12%) of 43 patients had lesions measuring 5–10 mm, which likely
explains the high accuracy of core needle biopsy
[11].
Some authors [12] assert
that 18F-FDG PET is sufficient for differentiating benign from
malignant solitary pulmonary nodules, a positive result determining the need
for lung resection. Although FDG PET can be helpful when a lung lesion is not
metabolically active, false-positive results are a problem in regions with a
high prevalence of granulomatous infection because they increase the rate of
unnecessary thoracotomy for benign disease
[3]. The diagnostic accuracy of
needle biopsy in the diagnosis of necrotizing granuloma has not been
previously reported, to our knowledge.
In our study, the sensitivity of FNA biopsy in the diagnosis of necrotizing
granuloma was 2%, and the sensitivity of core needle biopsy was 91%. These
findings correlate with those of previous studies in which FNA biopsy was
found to have low sensitivity (
50%) in the diagnosis of benign lung
nodules [6]. The low
sensitivity may be due to the nonspecific cytopathologic appearance of benign
disease coupled with a small amount of histopathologic material
[4]. Klein et al.
[4] found similar results in a
retrospective review of specific benign lesions diagnosed with core needle
biopsy. The sensitivity of FNA biopsy compared with core needle biopsy of
benign lesions in that series was 44% versus 100% (p <0.05)
[4]. In our series, FNA biopsy
was diagnostic of necrotizing granuloma in only one patient and had even lower
sensitivity than for other benign lung lesions. This finding contrasted to
those for core needle biopsy, which had a sensitivity of 91%. Only three
patients who underwent core needle biopsy needed open lung biopsy for
diagnosis. These findings support the essential role of core needle biopsy in
confirming the diagnosis of necrotizing granuloma and the inadequacy of FNA
biopsy in making this diagnosis. The presence of a cytotechnologist at biopsy
is helpful in converting FNA to core needle biopsy if the initial aspirates
appear acellular or insufficient.
Bronchoscopy is recognized as being less useful than TTNB in the accurate
diagnosis of solitary pulmonary lesions. The reported yield is as low as
28–31% for lesions smaller than 2 cm
[9] and increases with lesions
larger than 2 cm or in a central location
[13]. Our review supports
these findings. The findings at bronchoscopy were positive in only one of 18
patients. In our study, most lesions were 2 cm or smaller and in the periphery
of the lung and thus were difficult to diagnose at bronchoscopy.
It has been suggested [5,
9] that open lung biopsy is the
best initial procedure for a solitary lung lesion in a surgical candidate with
a high clinical probability of malignant disease. Most lung lesions for which
patients are referred for TTNB prove malignant, with an incidence of
80–85% [5]. At our
institution, thoracic surgeons are reluctant to operate on a patient with a
focal lung lesion without preoperative tissue diagnosis. Therefore, our
experience may not be representative of centers with a different clinical
approach. Because it is highly sensitive for malignant pulmonary tumors, FNA
biopsy is often sufficient for diagnosis, especially when a cytopathologist is
available to perform immediate review. According to the findings in our series
of cases, if the FNA biopsy finding is negative for malignancy, core needle
biopsy often results in a specific benign diagnosis and precludes unnecessary
thoracotomy.
In our study, the imaging characteristics of pulmonary necrotizing
granuloma on CT were indistinguishable from those of lung cancer. FNA was
insufficient for diagnosis, but core needle biopsy was highly sensitive (91%)
in the diagnosis of necrotizing granuloma and obviated invasive lung
resection.
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Abstract
Introduction
