Splenic Lymphangioma

Ioannis Ioannidis, MD; Andrea G. Kahn, MD

 Splenic lymphangioma is a rare malformation of the

splenic lymphatic channels, mostly seen in children. It is
characterized by the presence of cysts, resulting from
increases in the size and number of thin-walled lymphatic
vessels that are abnormally interconnected and dilated.
The condition may be restricted to the spleen, but in most
cases it involves multiple organs (systemic lymphangiomatosis). The clinical picture is variable; small lesions are
often incidentally detected through imaging studies, while
larger lesions can result in compression of organs, causing
pain or rupture even after minor trauma. Therefore,
splenic lymphangiomas should be considered in the
differential diagnosis of splenomegaly or left upper
quadrant pain even among adults and should be immediately treated with splenectomy; delay in the therapeutic
intervention can lead to life-threatening complications.
(Arch Pathol Lab Med. 2015;139:278282; doi: 10.5858/
arpa.2013-0656-RS)

ymphangiomas are benign malformations of the lymphatic system, usually found in the neck (75%) and
axilla (20%)1 and less commonly encountered in the orbit,
mediastinum, adrenal gland, kidney, bone, omentum,
gastrointestinal tract, retroperitoneum, liver, and pancreas.2,3 They were first described by Rodender in 1828;
however, the first case involving the spleen was reported
in 1885 by Frink.4,5 Between 1939 and 2010, only 189 cases
of splenic lymphangiomas were reported in the literature.6
Therefore, splenic lymphangiomas are considered uncommon benign tumors, occurring mainly in childhood, with
only a few cases reported in adults.7 In most patients, the
lymphangiomatous process involves additional sites in a
diffuse or multifocal fashion such as the liver, mediastinum,
and lung, the so-called lymphangiomatosis syndrome.7
Some cases of splenic lymphangiomas are associated with
synchronous or metachronous cystic hygroma of the neck.8
Isolated splenic lymphangiomas constitute a much rarer
form; only 9 cases between 1990 and 2010 were reported.9,10
Rarely, splenic lymphangiomas can be part of KlippelAccepted for publication December 27, 2013.
From the Department of Pathology, University of South Alabama,
Mobile.
The authors have no relevant financial interest in the products or
companies described in this article.
Presented in part as a poster at the College of American
Pathologists 2013 (CAP 13) Annual Meeting; October 13, 2013;
Orlando, Florida.
Reprints: Ioannis Ioannidis, MD, Department of Pathology,
University of South Alabama, Mobile, AL 36617 (e-mail:
iioannidis@health.southalabama.edu).
278 Arch Pathol Lab MedVol 139, February 2015

Trenaunay syndrome (characterized by varicose veins, bony

and soft tissue hypertrophy, cutaneous hemangiomas, and/
or malformations of the lymphatic system).11 Although no
consensus has yet been reached on whether splenic
lymphangioma is a neoplasm or a hamartoma, most
researchers support the latter opinion; its formation is
proposed to be due to abnormal congenital development of
lymphatic vessels.5 It can also be attributed to bleeding or
inflammation in the lymphatic system, which causes
obstruction and consequent lymphangiectasia.5,8,10
CLINICAL FEATURES
The clinical manifestations of splenic lymphangiomas are
usually related to the size of the spleen.8 In most cases,
isolated splenic lymphangiomas are asymptomatic and
incidentally detected through abdominal ultrasonography
or abdominal computed tomography. Large cystic lesions
can attain sufficient size to cause significant symptoms and
signs.8,12 The symptoms may include left upper quadrant
pain, loss of appetite, nausea, vomiting, and signs of
abdominal distension or a palpable mass. Most are usually
nonspecific and are due to compression of adjacent organs
such as the stomach, diaphragm, or kidney.8 Infection or
rupture of a lymphangioma can present as an acute
abdomen.8,13 Cases have been reported of larger lymphangiomas complicated by consumptive coagulopathy, bleeding, hypersplenism, and portal hypertension.8,14 The
pathophysiological consequences of a lymphangioma exceeding 3 to 4 kg can be diaphragmatic immobility and lung
atelectasis or pneumonia.8,13 Rarely, hypertension due to
compression of the renal artery by the splenic mass can be
seen.8,15
RADIOGRAPHIC FINDINGS
In terms of imaging characteristics, the spleen may be of
normal size, or splenomegaly can be present.8 Ultrasonography typically reveals cysts of various sizes (ranging from a
few millimeters to several centimeters in diameter).8 These
cystic lesions are hypoechoic or anechoic, with possible
septations.16 Minute echogenic calcifications may be identified.8 In one case report,16 a lymphangioma presented as a
mildly hyperechoic mass in the spleen.
Color Doppler ultrasonography can demonstrate the
vasculature of the mass (including the intrasplenic arteries
and veins along the cyst walls). It may assist in determining
the splenic origin by demonstrating the vessels at the splenic
hilum.8
Computed tomography usually shows low-density single
or multiple thin-walled sharply marginated subcapsular
cysts (Figure 1).16 Although no significant contrast enhanceSplenic LymphangiomaIoannidis & Kahn

Figure 1. Computed tomography showing an enlarged spleen

diffusely involving multiple low-attenuation lesions.

ment is typically seen, rare cases are reported in the

literature in which computed tomography of solid cystic
lymphangiomas showed no enhancement of the cysts but
demonstrated prominent enhancement of the solid components.16 The presence of curvilinear peripheral mural
calcifications is suggestive of cystic lymphangiomas but is
not a specific finding because it can also be seen in hydatid
cysts.8,17
On T1-weighted magnetic resonance imaging, the cystic
lesions can appear hypointense relative to the surrounding
viscera or hyperintense when filled with hemorrhagic or
proteinaceous material.7,8 On T2-weighted images, the mass
is characterized by multiloculated hyperintense areas that
correspond to the dilated lymphatic channels.7 The intervening septa are demonstrated as hypointense bands
because they bear abundant amounts of fibrous connective
tissue.8 The curvilinear peripheral mural calcifications seen
on computed tomography are difficult to identify on

magnetic resonance imaging. However, the high contrast

resolution of magnetic resonance imaging may help detect
the solid elements within the cystic lumen in the extremely
rare case in which malignant elements can be present.18 In
one case report,19 instead of the usual pattern of multiple
well-defined cystic lesions, there was diffuse involvement
replacing the entire spleen, with heterogeneous signal
intensities on T2-weighted images and heterogeneous
enhancement.
Finally, positron emission tomography is not routinely
used for the diagnosis of splenic lymphangiomas. However,
in a patient with 2 synchronous colon cancers that presented
with concomitant splenic mass (initially suspected to be
metastatic), it helped confirm that the lesion was benign by
revealing no fludeoxyglucose uptake.16
GROSS FINDINGS
Depending on the size of the lesion, the spleen may be
significantly enlarged or within normal limits. The macroscopic appearance of splenic lymphangioma is characterized
by a broad spectrum, including solitary nodules, multiple
nodules, and diffuse lymphangiomatosis.8 Because lymphatics are only found in the subcapsular region or in large
trabeculae, a solitary focal lymphangioma is most commonly
subcapsular and in some instances intraparenchymal. The
nodule usually consists of a single large cyst with a thick
fibrous wall or multiple various-sized thin-walled cysts with
honeycombing filled with clear fluid. Solid areas may be
seen, usually due to central scarring.4,20 Lymphangiomas
presenting as multiple nodules have similar-appearing
satellite lesions surrounding a larger lesion, are separated
by distinct residual splenic tissue, and can cause the spleen
to be nodular and enlarged.8 Cases of diffuse lymphangiomatosis can replace the spleen with expanding cysts that
result in little remaining normal parenchyma (Figure 2).15,21
Based on the size of the dilated lymphatic channels,

Figure 2. A, Diffuse splenic lymphangiomatosis presenting with multiple nodules that involve the entire splenic parenchyma. B, Cross-sections
reveal multiple cystic spaces of various diameters filled with serous fluid.
Arch Pathol Lab MedVol 139, February 2015

Splenic LymphangiomaIoannidis & Kahn 279

Figure 3. A, Diffuse splenic lymphangiomatosis presenting with multiple cysts surrounding a central solid area with scarring (hematoxylin-eosin
[H&E], original magnification 34). B, The cysts are filled with amorphous proteinaceous material (H&E, original magnification 310). C, The lining of
the cysts consists of attenuated endothelial cells (H&E, original magnification 340). D, The lining of the cysts is highlighted with the lymphatic
endothelial marker D2-40 (immunoperoxidase, original magnification 340).

lymphangiomas can be classified as capillary (supermicrocystic), cavernous (microcystic), or cystic (macrocystic).

Therefore, if the lymphangioma consists of lymphatics that
have the size of capillaries, it is classified as capillary
(microcystic), and if it consists of lymphatics that approach
the size of venules or veins, it is classified as cavernous
(microcystic) or cystic (macrocystic), respectively. This
nomenclature can be confusing as it is reminiscent of the
classification of hemangiomas, and because the distinction
is not always clear, it is not uniformly accepted among
pathologists.16,22
MICROSCOPIC FINDINGS
Histologic analysis reveals a single cyst or multiple cystic
structures (Figure 3, A) filled with eosinophilic amorphous
proteinaceous material (Figure 3, B) and lined by a flat layer
of attenuated endothelial cells (Figure 3, C).5,8 Rarely, the
lining of the cysts may form papillary projections.23 The wall
of the cysts ranges from thin and delicate to thick and
obviously fibrous. A varying number of macrophages or
lymphocytes can be found in the cystic spaces. The
surrounding parenchyma may be normal or show evidence
of congestion and fibrosis. Very few cases of splenic
280 Arch Pathol Lab MedVol 139, February 2015

lymphangiomas transforming into malignant lymphangiosarcomas have been reported.8 When atypical morphology
of the endothelium is present, careful long-term follow-up
observation of affected patients is recommended to determine whether these features indicate malignancy or simply
an unusual morphologic appearance of the endothelial
cells.8
Immunohistochemistry
When the histologic characteristics are not clear, the
endothelial origin of the cyst may be established with
immunohistochemical techniques to demonstrate reactivity
for CD31, CD34, factor VIII, podoplanin (D2-40), or vascular
endothelial growth factor receptor 3 (VEGFR-3).24 D2-40 is
a monoclonal antibody against dysgerminoma, observed to
selectively stain lymphatic endothelium (Figure 3, D). The
D2-40 antibody was also found to positively stain lymphangiomas but not benign tumors of blood vessels.24 It has
been suggested that VEGFR-3 immunopositivity indicates
partial lymphatic endothelial differentiation or, alternatively,
vascular endothelial growth factor C production by the
tumor cells that stimulate proliferation of adjacent lymphatics.24 On the other hand, factor VIII, CD31, or CD34
Splenic LymphangiomaIoannidis & Kahn

highlight endothelial cells in lymphatics and in blood

vessels.24
Electron Microscopy
Electron microscopy may assist in determining the
endothelial origin of the cells lining the cyst. It can highlight
the presence of rod-shaped microtubulated bodies (WeibelPalade bodies), which are the storage granules of endothelial cells.23
DIFFERENTIAL DIAGNOSIS
The differential diagnosis of splenic lymphangiomas
includes hemangiomas, true (splenic) epidermoid cysts,
mesothelial cysts, and parasitic cysts (most commonly due
to Echinococcus granulosus).25 Hemangiomas are characterized by vascular channels lined by endothelium, but they are
extensively filled with red blood cells instead of the
amorphous proteinaceous material of lymphangiomas. D240 positivity can assist in highlighting the lymphatic
endothelial differentiation; however, attention should be
given to the fact that D2-40 can also stain myoepithelial cells
of blood vessels.24 True splenic cysts will have definite
epithelial lining and will be positive for cytokeratin, while
the cells lining a mesothelial cyst will be positive for
mesothelial cell markers such as Wilms tumor 1 (WT-1)
and calretinin.26 To exclude a hydatid cyst in a patient with a
cystic splenic mass, a serologic test for Echinococcus should
be performed. If removed, the cyst will consist of 3 layers
(innermost germinal layer, intermediate laminated membrane, and outer fibrous layer) and contain protoscolices
(attached or separated) with a double row of refractile,
birefringent, acid-fast hooklets 22 to 40 lm in size and 4
round suckers that comprise the hydatid sand. Finally, in a
young patient with splenic lymphangioma, the diagnostic
evaluation should be extended to include extrasplenic organs
because it has been observed that in younger patients the
likelihood of multiorgan involvement is greater.8
TREATMENT AND PROGNOSIS
The treatment of choice for splenic lymphangiomas is
complete surgical resection because other therapeutic
modalities (aspiration, drainage, and irradiation) have
shown unsatisfactory results.27,28 Some investigators prefer
conservative treatment in the case of small asymptomatic
lesions detected incidentally, reserving splenectomy for
large, multiple, or symptomatic lesions.27,29 Partial resection
techniques have also been applied in cases of limited
disease; however, leaving a splenic remnant in cases of
diffuse involvement increases the risk of further growth and
enlargement, sometimes requiring a second operation.
Laparoscopic splenectomy is emerging as the procedure of
choice in patients with a normal to moderately enlarged
spleen but is considered a contraindication in patients with
massive splenomegaly.30 The most important aspect when
considering treatment options is that surgery should be
recommended immediately after the diagnosis has been
established to avoid complications such as infection,
hemorrhage, rupture, intestinal obstruction, and tumor
enlargement that may eventually prevent complete removal.27 The prognosis of splenic lymphangioma after resection
is favorable. The main complication is recurrence, which is
demonstrated in 9.5% of patients, frequently after incomplete resection.5
Arch Pathol Lab MedVol 139, February 2015

CONCLUSION
Splenic lymphangioma is a rare malformation of the
splenic lymphatic system, mostly seen in children and rarely
in adults. Although the etiology is still unclear, it is
considered more likely a hamartomatous process rather
than a neoplasm. Histologically, splenic lymphangioma is
characterized by the presence of cysts lined by attenuated
endothelial cells. The condition may involve only the spleen,
but in most cases it is part of a systemic malformation of
lymphatic channels that affects multiple organs (systemic
lymphangiomatosis). Most lesions are incidentally detected
through imaging studies, while larger lesions can cause
compression of adjacent organs, with various symptoms.
Therefore, splenic lymphangiomas should be considered in
the differential diagnosis of splenomegaly or left upper
quadrant pain even among adults because they are
amenable to curative treatment. Delay in their surgical
intervention may lead to severe complications such as
infection, rupture, and hemorrhage.
References
1. Kosir MA, Sonnino RE, Gauderer MW. Pediatric abdominal lymphangiomas: a plea for early recognition. J Pediatr Surg. 1991;26(11):13091313.
2. Davidson AJ, Hartman DS. Lymphangioma of the retroperitoneum: CT and
sonographic characteristic. Radiology. 1990;175(2):507510.
3. Chang WC, Liou CH, Kao HW, Hsu CC, Chen CY, Yu CY. Solitary
lymphangioma of the spleen: dynamic MR findings with pathological correlation.
Br J Radiol. 2007;80(949):e4e6. http://bjr.birjournals.org/content/80/949/e4.
long. Accessed January 10, 2013.
4. Avigad S, Jaffe R, Frand M, Izhak Y, Rotem Y. Lymphangiomatosis with
splenic involvement. JAMA. 1976;236(20):23152317.
5. Chung SH, Park YS, Jo YJ, et al. Asymptomatic lymphangioma involving the
spleen and retroperitoneum in adults. World J Gastroenterol. 2009;15(44):5620
5623.
6. Asch MJ, Cohen AH, Moore TC. Hepatic and splenic lymphangiomatosis
with skeletal involvement: report of a case and review of the literature. Surgery.
1974;76(2):334339.
7. Solomou EG, Patriarheas GV, Mpadra FA, Karamouzis MV, Dimopoulos I.
Asymptomatic adult cystic lymphangioma of the spleen: case report and review
of the literature. Magn Reson Imaging. 2003;21(1):8184.
8. Abbott RM, Levy AD, Aguilera NS, Gorospe L, Thompson WM. From the
archives of the AFIP: primary vascular neoplasms of the spleen: radiologicpathologic correlation. Radiographics. 2004;24(4):11371163.
9. Wadsworth DT, Newman B, Abramson SJ, Carpenter BL, Lorenzo RL.
Splenic lymphangiomatosis in children. Radiology. 1997;202(1):173176.
10. Patti R, Iannitto E, Di Vita G. Splenic lymphangiomatosis showing rapid
growth during lactation: a case report. World J Gastroenterol. 2010;16(9):1155
1157.
11. Jindal R, Sullivan R, Rodda B, et al. Splenic malformation in a patient with
Klippel-Trenaunay syndrome: a case report. J Vasc Surg. 2006;43(4):848850.
12. Komatsuda T, Ishida H, Konno K, et al. Splenic lymphangioma: US and CT
diagnosis and clinical manifestations. Abdom Imaging. 1999;24(4):414417.
13. Moir C, Guttman F, Jequier S, Sonnino R, Youssef S. Splenic cysts:
aspiration, sclerosis, or resection. J Pediatr Surg. 1989;24(7):646648.
14. Dietz WH Jr, Stuart MJ. Splenic consumptive coagulopathy in a patient
with disseminated lymphangiomatosis. J Pediatr. 1977;90(3):421423.
15. Economides NG, Benton BF, Fortner TM, Miles RM. Splenic pseudocysts:
report of two cases and review of the literature. Am Surg. 1980;46(11):644648.
16. Eghtedari M, Sicklick J, Kono Y, Peterson MR, Santillan CS. Unusual
imaging profile of a solitary splenic lymphangioma. Acta Radiol Short Rep. 2012;
1(8). http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3738359/. Accessed January
10, 2013.
17. Rasheed K, Zargar SA, Telwani AA. Hydatid cyst of spleen: a diagnostic
challenge. N Am J Med Sci. 2013;5(1):1020.
18. Feigenberg Z, Wysenbeek A, Avidor E, Dintsman M. Malignant lymphangioma of the spleen. Isr J Med Sci. 1983;19(2):202204.
19. Vanhoenacker FM, Schepper AM, Raeve H, Berneman Z. Cystic
angiomatosis with splenic involvement: unusual MRI findings. Eur Radiol.
2003;13(suppl 6):L35L39.
20. Chan KW, Saw D. Distinctive, multiple lymphangiomas of spleen. J Pathol.
1980;131(1):7581.
21. Park JY, Song KT. Splenic cyst: a case report and review of literature. Am
Surg. 1971;37(9):544547.
22. Yang F, Chen WX. Splenic lymphangioma that manifested as a solid-cystic
mass: a case report. World J Gastroenterol. 2013;19(5):781783.
23. Takayama A, Nakashima O, Kobayashi K, Kojiro M. Splenic lymphangioma
with papillary endothelial proliferation: a case report and review of the literature.
Pathol Int. 2003;53(7):483488.

Splenic LymphangiomaIoannidis & Kahn 281

24. Debelenko LV, Perez-Atayde AR, Mulliken JB, Liang MG, Archibald TH,
Kozakewich HP. D2-40 immunohistochemical analysis of pediatric vascular
tumors reveals positivity in kaposiform hemangioendothelioma. Mod Pathol.
2005;18(11):14541460.
25. Ferrozzi F, Bova D, Draghi F, Garlaschi G. CT findings in primary vascular
tumors of the spleen. AJR Am J Roentgenol. 1996;166(5):10971101.
26. Cibas ES. Pleural, pericardial, and peritoneal fluids. In: Cibas ES,
Ducatman BS, eds. Cytology: Diagnostic Principles and Clinical Correlates. 3rd
ed. Philadelphia, PA: Saunders; 2009:129153.

27. Yu X, Yu J, Liang P, Liu F. Real-time contrast-enhanced ultrasound in

diagnosing of focal spleen lesions. Eur J Radiol. 2012;81(3):430436.
28. Makrin V, Avital S, White I, Sagie B, Szold A. Laparoscopic splenectomy for
solitary splenic tumors. Surg Endosc. 2008;22(9):20092012.
29. Lam KY, Tang V. Metastatic tumors to the spleen: a 25-year clinicopathologic study. Arch Pathol Lab Med. 2000;124(4):526530.
30. Maurus CF, Schafer M, Muller
MK, Clavien PA, Weber M. Laparoscopic

versus open splenectomy for nontraumatic diseases. World J Surg. 2008;32(11):

24442449.

Prepare Now for the CAP 15 Abstract Program

Dont Wait! Plan now to submit abstracts and case studies for the College of American
Pathologists (CAP) 2015 meeting, which will be held October 4th Nashville, Tenn.
Submissions for the CAP 15 Abstract Program will be accepted from:

Monday, February 9, 2015 through 6 p.m. Central time

Friday, April 10, 2015
Accepted submissions will appear online on the Archives of Pathology & Laboratory
Medicine Web site as a supplement to the October 2015 issue. Visit the CAP 15 Web site at
http://www.cap.org/cap15 for additional abstract program information as it becomes
available.

282 Arch Pathol Lab MedVol 139, February 2015

Splenic LymphangiomaIoannidis & Kahn