A covert cause of hypoxemia: Intravascular pulmonary lympho
Published on Patient Care Online (http://www.patientcareonline.com)
A covert cause of hypoxemia: Intravascular pulmonary
lymphoma
October 23, 2008 | Journal Of Respiratory Diseases [1]
By Seth Koenig, MD [2], Tawfiqul A. Bhuiya, MD [3], Rubin Cohen, MD [4], and Leonard Rossoff, MD
[5]
We describe a patient with intravascular pulmonary lymphoma who presented with progressive
dyspnea and hypoxemia with normal chest radiographic findings. After an unrevealing noninvasive
evaluation, a high-grade B-cell intravascular lymphoma was diagnosed by bronchoscopy with
transbronchial biopsy. Treatment with a modified CHOP regimen resulted in resolution of the
patient’s hypoxemia and exercise limitation. Although intravascular pulmonary lymphoma rarely
presents with pulmonary symptoms, it should be considered in the differential diagnosis of patients
presenting with hypoxemia and normal chest radiographic findings.
We describe a patient with intravascular pulmonary lymphoma who presented with progressive
dyspnea and hypoxemia with normal chest radiographic findings. After an unrevealing noninvasive
evaluation, a high-grade B-cell intravascular lymphoma was diagnosed by bronchoscopy with
transbronchial biopsy. Treatment with a modified CHOP regimen resulted in resolution of the
patient's hypoxemia and exercise limitation. Although intravascular pulmonary lymphoma rarely
presents with pulmonary symptoms, it should be considered in the differential diagnosis of patients
presenting with hypoxemia and normal chest radiographic findings.
The case
A 55-year-old female nonsmoker presented with a chief complaint of 6 weeks of progressive severe
exertional dyspnea. She denied chest pain, cough, sputum production, hemoptysis, rash, arthralgias,
fever, night sweats, and chills. Two weeks before presentation, the patient noted fatigue and
weakness, with occasional diarrhea but no melena or hematochezia. Twenty years previously, she
had been treated for tuberculosis with a 6-month 4-drug regimen.
The patient's physical examination findings were unremarkable. Her heart rate and respiration rate
were normal at rest. Pulse oximetry showed an oxygen saturation of 88% on room air, and arterial
blood gas analysis revealed a PaO2 of 58 mm Hg. Her oxygen saturation rose to 95% on 2 L of
oxygen via nasal cannulae.
Chest radiographic and ECG findings were normal. The results of a ventilation-perfusion scan were
interpreted as very low probability for pulmonary embolism, and spirometry demonstrated a mild
obstructive defect. A high-resolution CT pulmonary angiogram showed minimal left apical scarring
consistent with well-healed tuberculosis.
The results of routine laboratory tests, including liver function tests, were normal, except for a
lactate dehydrogenase (LDH) level of 1409 U/L (normal, 185 to 290 U/L). Over the course of a few
days, generalized edema developed. The patient's aspartate aminotransferase level increased to
115 U/L (normal, 10 to 47 U/L), and her albumin level decreased to 2.6 g/dL (normal, 3.6 to 4.8 g/dL).
The results of a hepatitis profile and urinalysis were normal. An echocardiogram demonstrated
normal ventricular function and chamber sizes with a patent foramen ovale, although a significant
right-to-left shunt was not demonstrated.
Worsening hypoxemia prompted fiberoptic bronchoscopy with transbronchial biopsy. This revealed
an increased number of atypical cells within the blood vessels of the lung parenchyma, identified as
a clonal B-cell lymphoma (Figure). A diagnosis of intravascular pulmonary lymphoma was made. A
fluorodeoxyglucose positron emission tomography (FDGPET) scan revealed diffuse uptake in the
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A covert cause of hypoxemia: Intravascular pulmonary lympho
Published on Patient Care Online (http://www.patientcareonline.com)
Figure – Capillaries in the interalveolar septae are filled with large, atypical lymphocytes
(hematoxylin-eosin stain, left). The immunohistochemical study shows atypical lymphocytes that are
strongly positive for CD20 (right).
lung.
A modified CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) regimen was started, and
the patient had dramatic clinical improvement. Her hypoxemia resolved, and she had no significant
desaturation with exertion. The results of complete lung function tests were normal, and another
FDG-PET scan showed resolution of the increased lung activity.
Discussion
A clinical complex of dyspnea, hypoxemia, and normal chest radiographic findings is frequently
encountered by physicians. The history, physical examination, and basic noninvasive evaluation
usually establish the diagnosis. Common diseases with this presentation include reactive airway
diseases, chronic obstructive pulmonary disease, and pulmonaryembolism. Less common entities
include hemoglobinopathies, right-to-left shunts, and early interstitial lung disease.
Our patient presented with exertional dyspnea, oxygen desaturation, and normal imaging findings.
Her echocardiographic and CT angiographic findings made intrapulmonary or intracardiac shunting
unlikely. The normal chest CT findings made interstitial lung disease improbable.1
The patient's evaluation did not include measurement of carbon monoxide–diffusing capacity
(DLCO). Her DLCO probably would have been reduced, but a reduced DLco would not have
discriminated interstitial lung disease from pulmonary vascular disease. An FDGPET scan confirmed
a metabolically active diffuse process within the lung, and transbronchial biopsy revealed the
diagnosis of an intravascular lymphoma.
Intravascular lymphoma is a rare extranodal lymphoma characterized by the proliferation of
lymphocytes within the vascular lumen. It is usually a B-cell lymphoma and is classified as
high-grade. Intravascular lymphoma was initially thought to be of endothelial origin and named
angioendotheliomatosis proliferans systematica. Advances in cell-specific markers demonstrated its
lymphocytic origin.2,3 Clinical signs and symptoms are predominantly neurological and
dermatological and result from the eventual obliteration of specific vascular beds.
The diagnosis of intravascular lymphoma is challenging because the symptoms and signs are
nonspecific and heterogeneous. Primary pulmonary symptoms are exceedingly rare.4 In one report,
the patient had dyspnea, fatigue, fever, an increased LDH level, and what appeared to be atelectasis
on a CT scan, and the diagnosis of intravascular lymphoma was based on biopsy results.5
Another patient presented with pulmonary hypertension and nonspecific pulmonary infiltrates, which
resolved with treatment.4 Intravascular lymphoma should be considered in the differential diagnosis
of pulmonary hypertension when more common causes have been ruled out. Other pulmonary
radiographic manifestations include air trapping with a mosaic pattern on a CT scan and diffuse
interstitial markings.
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A covert cause of hypoxemia: Intravascular pulmonary lympho
Published on Patient Care Online (http://www.patientcareonline.com)
The current treatment of intravascular lymphoma is a modified CHOP regimen. In one case series,
32% of patients who received a modified CHOP regimen had an overall survival of 3 years.6 Within 1
month of receiving this regimen, our patient no longer required supplemental oxygen and her edema
resolved. Subsequent LDH levels and FDG-PET scan results have remained normal, and she is back
at work.
We believe that this is a unique presentation of intravascular pulmonary lymphoma with solely
pulmonary symptoms, hypoxemia, and no radiographic abnormalities. Therefore, this entity should
be included as a rare cause of the frequently encountered combination of dyspnea, hypoxemia, and
normal radiographic findings.
References: REFERENCES
1. Orens JB, Kazerooni EA, Martinez FJ, et al. The sensitivity of high-resolution CT in detecting
idiopathic pulmonary fibrosis proved by open lung biopsy. A prospective study. Chest.
1995;108:109-115.
2. Willemze R, Kruyswijk MR, De Bruin CD, et al. Angiotropic (intravascular) large cell lymphoma of
the skin previously classified as malignant angioendotheliomatosis. Br J Dermatol.
1987;116:393-399.
3. Molina A, Lombard C, Donlon T, et al. Immunohistochemical and cytogenetic studies indicate that
malignant angioendotheliomatosis is a primary intravascular (angiotropic) lymphoma. Cancer.
1990;66:474-479.
4. Owa M, Koyama J, Asakawa K, et al. Intravascular lymphomatosis presenting as reversible severe
pulmonary hypertension. Int J Cardiol. 2000;75:283-284.
5. Chim CS, Choy C, Ooi GC, et al. Two unusual lymphomas. Case 2: pulmonary intravascular
lymphomatosis. J Clin Oncol. 2000;18:3733-3735.
6. Ferreri AJ, Campo E, Seymour JF, et al. Intravascular lymphoma: clinical presentation, natural
history, management and prognostic factors in a series of 38 cases, with special emphasis on the
"cutaneous variant." Br J Haematol. 2004;127:173-183.
Source URL:
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Links:
[1] http://www.patientcareonline.com/journal-respiratory-diseases
[2] http://www.patientcareonline.com/authors/seth-koenig-md
[3] http://www.patientcareonline.com/authors/tawfiqul-bhuiya-md
[4] http://www.patientcareonline.com/authors/rubin-cohen-md
[5] http://www.patientcareonline.com/authors/leonard-rossoff-md
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