Rare disease

Case report

Recurrent chylothorax: a clinical mystery

Eva Otoupalova,1 Shaiva Ginoya Meka,1 Sanjay Dogra,2 Bhavin Dalal2

1
Department of Internal Summary Pleural fluid triglyceride level over 110 mg/dL
Medicine, Beaumont Health Chylothorax is an unusual cause of pleural effusion, is diagnostic of chylothorax; however, 15% of
System, Royal Oak, Michigan, typically caused by trauma or malignancy. Waldenstrom’s chylothoraces can have lower triglyceride levels.8
USA
2 macroglobulinaemia (WM) is a clinicopathological entity Lipoprotein electrophoresis of the pleural fluid
Department of Pulmonary
demonstrating lymphoplasmacytic lymphoma in the bone showing chylomicrons is confirmatory in uncertain
and Critical Care Medicine,
Beaumont Health System, Royal marrow with an IgM monoclonal gammopathy in the cases.9 Cholesterol is usually <200 mg/dL; higher
Oak, Michigan, USA blood. Recurrent chylous effusions are often resistant levels are typical for cholesterol effusion.10
to conservative treatment and may require surgical Treatment of chylothorax consists of treatment
Correspondence to intervention. We present a unique case of a 50-year- of the underlying aetiology, a low-fat diet and
Dr Shaiva Ginoya Meka, old woman with recurrent chylothorax secondary to drainage. Octreotide/somatostatin and etilefrine
​Shaiva.​Ginoya@​beaumont.​edu WM that completely resolved with ibrutinib therapy. To therapy might be highly efficacious in conserva-
EO and SGM contributed our knowledge, this is the eighth such case reported in tive management. Recurrent chylothorax often
equally. literature and the first case of successful resolution of requires surgical treatment such as thoracic duct
chylothorax with monoclonal antibody therapy. ligation, talc pleurodesis or pleuroperitoneal
Accepted 3 September 2017 shunt placement.11 Lymphatic interventions have
recently emerged as a new frontier for interven-
tional radiologists.12
Background Waldenstrom’s macroglobulinaemia (WM) is a
Pleural effusion is a common clinical problem, with rare disorder with an annual incidence of approx-
estimated 1–1.5 million new cases in the USA each imately three per million people.13 14 It is char-
year.1 It is defined as an excess of fluid in the pleural acterised by the presence of lymphoplasmacytic
cavity and is a consequence of imbalance of pleural lymphoma in the bone marrow with an IgM mono-
fluid production, absorption or both. Chylothorax clonal gammopathy in the blood. Bone marrow
is a rare cause of pleural effusion that results from examination in WM should demonstrate at least
thoracic duct damage with chyle leakage from the 10% of infiltration by small lymphocytes with
lymphatic system into the pleural space. Chylotho- lymphoplasmacytic features or lymphoplasmacytic
races contain a high concentration of triglycerides lymphoma. The other requisite pathological feature
in the form of chylomicrons, lymphocytes and of WM is the hypersecretion of a monoclonal IgM
immunoglobulins. paraprotein.15 16
Iatrogenic injury from thoracic surgery is the Symptoms of WM are related to infiltration
most common traumatic cause, while non-trau- of haematopoietic tissues or effects of mono-
matic causes include various aetiologies such as clonal IgM in the blood. IgM paraprotein can
malignancy, sarcoidosis, amyloidosis, congen- cause various symptoms resulting from systemic
ital duct abnormalities and diseases of the amyloidosis, paraprotein depositions in the
lymph vessels such as yellow nail syndrome and organs, cryoglobulinaemia, peripheral neurop-
lymphangioleiomyomatosis.2–4 athy and hyperviscosity syndrome. Hypervis-
Clinically, dyspnoea, chest pain and cough are the cosity can cause neurological symptoms such as
most common symptoms of chylothorax. Malnutri- blurring of vision, headache, vertigo, confusion,
tion from loss of protein and immunosuppression stroke or coma. About 20% to 25% of patients
from loss of immunoglobulins into pleural space with WM develop peripheral neuropathy from
might lead to weight loss and infections.5 sensory demyelination related to antimyelin-as-
Imaging typically shows pleural effusion that sociated glycoprotein antibody.
is most often right-sided due to the anatomy of Rituximab is commonly used as first-line treat-
thoracic duct. Thoracic duct crosses from the right ment of symptomatic patients; however, novel
to left posterior mediastinum at level of T5; thus, immunotherapies such as recently approved tyro-
damage to the duct above T5 typically leads to left- sine kinase inhibitor ibrutinib are emerging.15
sided effusion, whereas damage below leads to a We present a unique case of recurrent
right-sided effusion.6 chylothorax secondary to WM. The pathogen-
Pleural fluid appearance might be the first clue to esis of chylothorax in our case is believed to
diagnosing chylothorax. The appearance of fluid from be compression of thoracic duct by an enlarged
To cite: Otoupalova E, a chylothorax is typically milky; however, it can be mediastinal lymph node. To our knowledge,
Meka SG, Dogra S, et al. BMJ
Case Rep Published Online serous or sanguineous.7 Cholesterol pleural effusion this is the seventh such case reported in liter-
First: [please include Day and empyema might appear similar. Supernatant of the ature and the first case of successful resolu-
Month Year]. doi:10.1136/ pleural fluid from a chylothorax typically fails to clear tion of chylothorax with monoclonal antibody
bcr-2017-220750 after centrifugation, whereas empyema fluid clears.8 therapy.
Otoupalova E, et al. BMJ Case Rep 2017. doi:10.1136/bcr-2017-220750 1
 Rare disease

Figure 1  Chest radiography depicting the moderate right-sided pleural effusion. (A) posteroanterior view, (B) lateral view.

Case presentation chylothorax. Flow cytometry of the pleural fluid showed that
A 50-year-old Caucasian woman presented to the emergency 3% of total cells were monotypic B cells, expressing CD19,
department with right-sided pleuritic chest that began 1 day CD20, CD45 and kappa light chain but were negative for CD5
prior. She had noted progressive dyspnoea for the past month. and CD10. The T cells (36% of total cells) showed a CD4:CD8
She denied any other associated symptoms such as fever, weight ratio of 4.8:1, with normal expression of CD5. Cytology of
loss, fatigue, lymphadenopathy, nausea or vomiting. fluid revealed moderately cellular effusion with abundant small
Her medical history was significant for WM, discovered 3 years lymphocytes mixed with a few reactive mesothelial cells. Find-
ago. She was found to have low-grade B-cell non-Hodgkin’s ings were consistent with B-cell lymphoma.
lymphoma, most consistent with lymphoplasmacytic lymphoma,
with 20%–30% bone marrow involvement and elevated serum Outcome and follow-up
IgM kappa levels. She was asymptomatic during these past Following thoracentesis, she had slight improvement in her
3 years and was observed without any specific treatment. shortness of breath. She was also started on a fat-free diet.
In the emergency department, she was found to be normo- However, she developed re-accumulation of pleural fluid several
tensive and did not have signs of respiratory failure. Physical days later and required second thoracentesis with pigtail catheter
examination revealed palpable adenopathy in bilateral anterior placement. Repeat fluid analysis showed decreasing triglycerides
cervical as well as the left supraclavicular region. Her lung exam- to 94 mg/dL and negative cultures. She was discharged in stable
ination revealed absent breath sounds in the right lower lobe. condition; pigtail catheter was removed prior to discharge.
Cardiovascular and abdominal examinations were unremarkable. The patient was followed as outpatient by oncology. She
underwent repeat bone marrow biopsy 1 month later, which
Investigations demonstrated hypercellular marrow with 90% infiltrate of
Initial laboratory studies revealed total white cell count 5.8 small-to-intermediate lymphocytes and plasma cells. Flow
x109, mild lymphopaenia 1.0 bil/L, anaemia with Hb 10.2 g/
dL, normal renal function along with a low anion gap and low
albumin. Serum protein electrophoresis revealed IgM kappa
monoclonal protein with a total IgM level of 82 mg/dL.
Initial chest X-ray demonstrated a right pleural effusion
(figure 1). A CT chest was subsequently performed and showed
a large right-sided pleural effusion with associated compressive
atelectasis and slight mediastinal shift to the left. Additionally, it
demonstrated adenopathy in the lower neck and upper thorax,
which was increased in size compared with CT scan from 3 years
ago. Lymphadenopathy was also noted at the thoracic duct, near
the confluence of the left subclavian left internal jugular veins
(figure 2).

Treatment
The patient underwent thoracentesis and 1.4 L of milky fluid was
removed. Pleural fluid differential showed total white cell count
of 13 140/mcL, red blood cell count 4000/mcL, 75% neutrophil Figure 2  Chest CT demonstrating lymphadenopathy at the thoracic
count, 22% lymphocytes and monocytes 3%. Analysis of pleural duct, near the confluence of the left subclavian and internal jugular
fluid showed elevated triglycerides of 319 mg/dL consistent with veins (arrow).
2 Otoupalova E, et al. BMJ Case Rep 2017. doi:10.1136/bcr-2017-220750
 Rare disease
cytometry of marrow showed a population of B cells positive partial response, 36 partial response, 11 minor response, none
for CD19, CD20, CD23 and surface immunoglobulin kappa complete).25 Such immunotherapy agents may allow treatment
consistent with extensive infiltration by B-cell lymphoma. She of WM-related—and perhaps other malignancy-related—
was started on ibrutinib 420 mg every night. Her pleural effu- chylothorax without necessitating surgical intervention.
sion resolved within 2 months and she did not need any further Contributors  EO and SGM contributed equally to the creation of this manuscript
thoracentesis. including the acquisition of data and its interpretation/analysis. SD and BD assisted
in the overall planning, revisions and providing insights to the discussion. All four
authors agree to account for this manuscript.
Discussion
Competing interests  None declared.
WM as a cause of chylothorax has previously been only described
in seven cases in literature.17–23 In the only other case in English Patient consent  Obtained.
literature by Poisson et al, the patient was an 82-year-old man Provenance and peer review  Not commissioned; externally peer reviewed.
with a known diagnosis of WM and had moderate infiltration Open Access  This is an Open Access article distributed in accordance with the
of bone marrow with lymphoma.17 Similar to our case, he Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which
presented with dyspnoea and large pleural effusion. CT imaging permits others to distribute, remix, adapt, build upon this work non-commercially,
and license their derivative works on different terms, provided the original work
revealed lymphadenopathy in the left posterior costomediastinal is properly cited and the use is non-commercial. See: [Link]
angle associated with a predominantly left-sided effusion. He licenses/​by-​nc/​4.​0/
was treated with rituximab, cyclophosphamide and dexameth- © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article)
asone with resolution of the chylothorax. 2017. All rights reserved. No commercial use is permitted unless otherwise expressly
The predominant mechanism in malignancy-induced granted.
chylothorax is thoracic duct obstruction. Mediastinal lymphade-
nopathy compresses the lymphatic vessels and prevents drainage References
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Otoupalova E, et al. BMJ Case Rep 2017. doi:10.1136/bcr-2017-220750 3

Rare disease

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4 Otoupalova E, et al. BMJ Case Rep 2017. doi:10.1136/bcr-2017-220750