(Chest. 2001;120:1027-1030.)
© 2001
American College of Chest Physicians
Pulmonary Small Lymphocytic Lymphoma (Mucosa-Associated Lymphoid Tissue Type) Associated With Pulmonary Hyalinizing Granuloma*
Yafei Ren, MD, PhD;
ElizabethAnn N. Raitz, MD;
Kyo Rak Lee, MD;
Susan K. Pingleton, MD, FCCP and
Ossama Tawfik, MD, PhD
*
From the Departments of Pathology and Laboratory Medicine (Drs. Ren and Tawfik), Internal Medicine (Drs. Raitz and Pingleton), and Radiology (Dr. Lee), University of Kansas Medical Center, Kansas City, KS.
Correspondence to: Ossama Tawfik, MD, PhD, Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, 3901 Rainbow Blvd, Kansas City, KS 66160; e-mail: otawfik{at}kumc.edu
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Abstract
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A case of pulmonary hyalinizing granuloma (PHG) and concomitant
low-grade, small lymphocytic lymphoma of the lung is presented. This is
the first occurrence of pulmonary lymphoma in patients with PHG ever
reported. The infiltrates around a left lower lobe nodule with left
pleural effusion and thickening seen on chest CT were histologically
proven to be lymphomatous infiltrates of the lung, pleura, and chest
wall muscle. We believe that the lymphoma developed around the nodule
and spread to the pleura and muscle in our patient. When infiltrates
around the nodules, pleural effusion, or adenopathy are developed
in a patient with proven PHG, close follow-up, biopsy, or careful
cytology should be seriously considered to rule out a developing
lymphoma.
Key Words: mucosa-associated lymphoid tissue lymphoma • non-Hodgkin’s lymphoma • pulmonary hyalinizing granuloma • pulmonary lymphoma • small lymphocytic lymphoma
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Introduction
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Pulmonary
hyalinizing granuloma (PHG) is a rare etiology of lung nodules. Since
the first report by Engleman et al1
in 1977, to the best
of our knowledge, 61 cases of PHG have been reported in the
English-language literature.2
3
4
5
6
7
The nodules are typically
benign in histology and clinical course, but slowly grow in size and
number. Because of their behavior and to rule out a malignancy, biopsy
is required to establish the primary diagnosis of PHG. The occurrence
of small cell-type malignant disease, specifically lymphoma in this
condition, has long been postulated, but only one case with PHG
associated with stage IV diffuse lymphocytic lymphoma of the abdomen
has been reported.5
We present the first case of PHG and
concomitant low-grade small lymphocytic B lymphoma of the lung.
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Case Report
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A 50-year-old Syrian man was referred to our medical center in
September of 1997 for follow-up of biopsy-proven PHG. Five months prior
to that, he presented to St. John’s Hospital in Detroit, MI, with a
chief complaint of dry cough and anterior chest pain with exertion.
Chest CT scans at St. John’s Hospital demonstrated multiple bilateral
pulmonary nodules. The largest nodule in right lower lobe measured
5 x 3.5 cm, and the nodule in the left lower lobe measured
1.8 x 1.6 cm (Fig 1
, top). There was minimal bilateral pleural thickening
without effusion. The largest nodule was removed and proved to be PHG.
Microscopically, the nodule was composed of dense fibrous stroma and
scarred vessels (Fig 2
). A characteristic rim of a moderate amount of lymphocytic infiltrate
with occasional lymphoid follicles and a few plasma cells was noted
around both nodules. Rare areas of calcification and necrosis were
noted within the nodules (Fig 2)
. Fungal, acid-fast, and Congo red
(amyloid) stain findings were negative. All culture findings were
reported negative as well.
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Figure 1.. Top: Initial CT scan at the
lower-thoracic level demonstrated four nodules, three in the right lung
and one in the left lung. The largest nodules in the right lower lobe
measured 5.0 x 3.5 cm and showed irregular, central calcification.
The left lower lobe nodule (arrow) measured 1.8 x 1.6 cm.
Bottom: Follow-up CT scan prior to surgery at the same
level demonstrated that the left lower lobe nodule increased in size to
3.1 x 2.0 cm. Note the infiltrate around the left lower lobe nodule
extending to the pleura laterally (arrow) with parietal pleural
thickening (curved arrow) and effusion.
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Figure 2.. PHG. Top left, A:
Well-circumscribed nodule of hyalinized center and a wreath of
lymphoplasmacytic infiltrate at the periphery (hematoxylin-eosin,
original x 40). Top right, B:
Higher-power view showing the characteristic thick ropy collagen
bundles adjacent to a lymphoid aggregate (hematoxylin-eosin,
original x 400). Rare areas of acute inflammation and calcification
are also noted in bottom left, C and
bottom right, D, respectively
(hematoxylin-eosin, original x 200 and original x 100,
respectively).
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At presentation to our institution, the patient was without shortness
of breath, cough, sputum production, or hemoptysis, and he denied chest
pain, weight loss, fever, or chills. He was born in Syria but had lived
most of his adult life in United States. He had not received Bacille
Calmette-Guérin vaccination and had no known drug allergies. His
medical history was noncontributory. He did not have any occupational
exposures that would place him at risk for pulmonary
complications.
On physical examination, the lungs were symmetrical in movement,
slightly dull to percussion in the left lower lung, and clear to
auscultation with no egophony. Findings of heart and abdominal
examination were normal. Pulmonary function tests performed at our
institution revealed FVC of 3.27 L (73% predicted),
FEV1 of 2.34 L (64% predicted), and
FEV1/FVC ratio of 72% (81% predicted).
A chest CT was repeated in September of 1997, which showed enlarging
bilateral multiple nodules of variable sizes ranging from 0.6 to 3 cm
with irregular borders and interval small pleural effusion compared to
the previous CT study (March 1997). His follow-up chest CT in December
of 1997 showed the nodules were more spiculated with an irregular
border and slight increase in size from the initial study. The left
lower lobe nodule showed an interval increase up to 3.1 cm with an
infiltrate extending to the pleura peripherally (Fig 1
,
bottom). There was interval progression in the thickening of
the parietal pleura. It was suggested that the findings may represent
an active phase of PHG or associated with another etiology, such as an
infectious or a malignant process. Cytologic examination of the left
pleural effusion fluid showed marked lymphocytosis with small atypical
lymphocytes. Flow-cytometric analysis was of limited value due to poor
cell viability. A diagnosis of lymphoproliferative disorder was
proposed. Accordingly, video-assisted thoracoscopic lung and pleural
biopsies were performed. Intraoperative findings showed the left lower
lobe nodule was firm and the surrounding parietal pleura was thickened.
The resected lung nodule measured 2.5 x 1.8 x 1.7 cm, and was
microscopically similar to the previous material and consistent with
PHG. Repeat fungal, acid-fast, and Congo red stain findings were
negative. All culture findings were negative. The adjoining lung tissue
showed multiple nodules of monotonous-appearing small atypical
lymphocytes most consistent with low-grade small lymphocytic lymphoma
of the mucosa-associated lymphoid tissue type (Fig 3
). Likewise, the left parietal pleura and chest wall in the region of
lung biopsy were heavily infiltrated by lymphoma cells (Fig 2
,
top right, B and bottom left,
C). Immunohistochemical studies confirmed the diagnosis with
the lymphoma cells staining positively for CD20 (L26, pan B marker) and
CD43 (Leu 22, pan B marker), and negative for CD3 (pan T marker). The
postoperative course was uneventful. The patient was discharged 6 days
after surgery. The patient was closely followed up for 2 years with
minor deterioration of his symptoms until September 2000, when
chemotherapy was initiated in Ann Arbor, MI. He received
cyclophosphamide, vincristine, and prednisone, and reported improvement
in his symptoms as well as a reduction of his PHGs by 50% of their
original size.
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Figure 3.. Small lymphocytic lymphoma (mucosa-associated
lymphoid tissue type) involving the lung and pleura.
Left: Nodular aggregates of lymphocytic cells in the
lung (hematoxylin-eosin, original x 40). Center:
Higher-power view showing a diffuse infiltrate of monotonous small
lymphocytes (hematoxylin-eosin, original x 400).
Right: Pleural involvement by lymphoma
(hematoxylin-eosin, original x 100).
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Discussion
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PHG is a rare entity that is considered to be a benign process. It
is usually diagnosed in the workup of a single or multiple nodules on
chest radiography. There are only 61 reported cases in the
English-language literature. Clinically, the majority of patients
presented with symptoms including cough, dyspnea, and pleuritic pain.
The remaining patients were asymptomatic and in whom the lesions were
seen on routine health-screening examinations. Our patient was slightly
older that the average age of 42 years (range, 19 to 77 years). The sex
distribution is approximately equal with no racial predominance.
The primary diagnosis of PHG cannot be made solely from the radiologic
features. The chest radiographs show either single, or more often
multiple, unilateral or bilateral nodules ranging from 0.2 to 15 cm in
size with an average size of 2.0 cm. As seen on CT in our patient, they
are randomly distributed in one or both lungs with no specific
predilection. The nodules characteristically show spiculated,
ill-defined borders with or without calcification or necrosis within
them, and with slow interval growth in many cases. The doubling time
was reported as 1 year in one case.6
It has been suggested
that when the nodules are located near the hilum or mediastinum,
fibrosing mediastinitis may be prone to develop.4
6
This
is the most common complication that developed in patients with PHG.
The nodule in the left lower lobe in our patient showed more irregular
infiltrative changes around it with associated pleural effusion and
thickening. These were histologically proved to be due to lymphomatous
involvement. The radiologic differential diagnoses included primary or
metastatic neoplasms, sarcoid and rheumatoid nodules, amyloidosis,
Wegener’s granulomas, and granulomas from tuberculosis or fungal
infections.
The histopathologic findings and pathologic differential diagnosis of
PHG have been well described by many researchers.1
2
4
6
The lesions characteristically consist of central concentric or
haphazard hyaline lamellae, and as peripheral rim of plasma cells and
lymphocytic infiltrate with occasional lymphoid follicles. In early
active lesions, the cellular components predominate, while the
collagenous lamellar bands are more prominent in old chronic lesions.
The increase of plasma cells, lymphocytes, and other inflammatory cells
corresponds with the spiculated, ill-defined border and progressive
growth of the nodules seen on chest radiograph and CT. The stimulus
triggering these progressive changes is unknown, and the pathogenesis
of PHG has not been well understood as well. Since sclerosing
mediastinitis, retroperitoneal fibrosis, rheumatoid arthritis, uveitis,
and ocular papillitis have been frequently associated with PHG, it has
been hypothesized that all of these conditions may present essentially
the same reactive response of an immunologic mechanism triggered by
histoplasma organisms, tuberculosis bacilli, or other infectious
agents.1
2
3
4
6
Neoplastic disease associated with PHG has rarely been reported. These
include abdominal lymphoma, multiple myeloma, Paget’s disease of the
breast, and astrocytoma of the brain.5
7
The case with
lymphoma was that of a female patient who presented with abdominal mass
and multiple pulmonary nodules. A stage IV diffuse lymphocytic lymphoma
was diagnosed with a laparotomy, and the lung nodules were presumed to
be metastasis without biopsy. Nine years later, the patient developed
proven plasmacytoma of the rib and abnormal bone marrow with 25%
plasma cells and many atypical forms and areas of marrow replacement by
plasma cells in sheets. She died 2 years later, and the postmortem
studies showed multiple PHG, amyloid deposits in multiple organs, but
no evidence of lymphoma in the lungs or elsewhere. It was concluded
that the occurrence of two different small cell neoplasms and PHG may
be a coincidence, but raised the possibility of transformation from one
B-cell neoplasm to another. The low-grade lymphocytic lymphoma in our
patient may be a coincidental occurrence with PHG. However, one can
postulate that a transformation from lymphocytes or lymphoid follicles
around the nodule to lymphocytic lymphoma is possible on the basis of
the histopathologic changes. Further investigation and future reports
of similar cases are desirable to support our proposal. As seen in our
patient, associated findings such as pleural changes, infiltrates
around the nodule, or hilar or mediastinal adenopathy may be the signs
suggesting a developing malignant disease, specifically small cell type
neoplasm, and more careful evaluation may be warranted in the patients
with proven PHG. Close follow-up, biopsy, and careful cytology of the
aspirated pleural effusion should be considered in these instances.
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Footnotes
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Abbreviation: PHG = pulmonary hyalinizing granuloma
Received for publication July 27, 2000.
Accepted for publication February 14, 2001.
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References
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Engleman, P, Liebow, AA, Gmelich, J, et al (1977) Pulmonary hyalinizing granuloma. Am Rev Respir Dis 115,997-1008[ISI][Medline]
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Guccion, JG, Rohatgi, PK, Saini, N (1984) Pulmonary hyalinizing granuloma: electron microscopic and immunologic studies. Chest 85,571-573[Abstract/Free Full Text]
-
Schlosnagle, DC, Check, IJ, Sewell, CW, et al (1982) Immunologic abnormalities in two patients with pulmonary hyalinizing granuloma. Am J Clin Pathol 78,231-235[ISI][Medline]
-
Yousem, SA, Hochholzer, L (1987) Pulmonary hyalinizing granuloma. Am J Clin Pathol 87,1-6[ISI][Medline]
-
Drasin, H, Blume, MR, Rosenbaum, EH, et al (1979) Pulmonary hyalinizing granulomas in a patient with malignant lymphoma, with development nine years later of multiple myeloma and systemic amyloidosis. Cancer 44,215-220[CrossRef][ISI][Medline]
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Chalaoui, J, Gregoire, P, Sylvestre, J, et al (1984) Pulmonary hyalinizing granuloma: a cause of pulmonary nodules. Radiology 152,23-26[Abstract/Free Full Text]
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Anazawa, Y, Hiromi, N, Motomiya, M, et al (1992) A case of pulmonary hyalinizing granuloma. Tohoku J Exp Med 167,39-45[ISI][Medline]
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Abstract
Introduction
