Immunohistochemistry Case Examples
Allen M. Gown
Anthony S.Y. Leong
Section 3 -
Splenic Angiomatoid Nodular Transformation (SANT) and Lymphangioma
Anthony S.Y. Leong
University of Newcastle
A 60-year-old man presented with pain in the left upper abdomen and splenomegaly and was clinically
diagnosed with metastatic tumor in the spleen. The 205g, 650 x 550 x 870mm spleen contained a relatively
well defined 40 x 40 x 40mm mass, composed of rounded nodules of varying sizes with the appearance and
colour of splenic tissue, encircled by grey fibrous septae. A separate 10mm subcapsular excrescence of
small cystic spaces was found away from the main tumor mass.
Microscopically, the nodules were confluent and of varying sizes composed of concentric spindle cells
and collagen (Figs 1 & 2) with lymphocytes, macrophages, plasma cells and siderophages interspersed
between the collagen (Fig 3). There were randomly placed slit-like, oval and irregular branching
vascular spaces lined by somewhat prominent endothelial cells within these nodules (Figs 4 & 5).
The angiomatoid nodules were formed of concentric layers of SMA positive myogenic cells with a lining
of fragmented basal lamina of irregular thickness similar to that of smooth muscle cells. The
endothelial cells were consistently positive for CD31 but showed variable staining for CD34 and less
frequently for CD8. There was no mitotic activity and nuclear atypia was not a feature of the lesion.
The separate subcapsular excrescence of cystic spaces was a lymphangioma filled with pale fluid and
lined by plump endothelial cells (Fig 6).
Diagnosis: Spleen (205g) – splenic angiomatoid nodular transformation (SANT) and lymphangioma
This entity is sufficiently distinctively both at macroscopic and microscopic level to earn the name
of 'sclerosing angiomatoid nodular transformation' (SANT).  In their report of 25 cases,
Martel et al  considered these lesions to be benign vascular processes apparently unique to
the spleen. The nodules are composed of vessels that replicate those in the normal splenic red pulp as
recognised by their phenotype capillaries being CD34+/CD8-/CD31+, sinusoids CD34-/CD8+/CD31+ and veins
CD34-/CD8-/CD31+. A recent case report has included positivity for CD68, not shown in the earlier
paper.  Similar lesions have previously been reported under the rubric of 'multinodular
hemangioma, splenic hamartoma, 
and splenic hemangioendothelioma.  The
differential diagnosis of SANT includes hemangioma and littoral angioma but these lesions are composed of
single rather than multiple types of blood vessels and lack the distinctive morphological features of
SANT both grossly and microscopically. Splenic hemangiomas are composed of conventional blood vessels of
the CD34+/CD31+, CD8- phenotype. Littoral cell angioma was said to be composed of vascular channels
lined by littoral cells or sinusoidal lining cells of the CD34-/CD8+/CD31+ phenotype and of separate
nodules with a prominent pseudopapillary growth pattern and absence of sclerosis. Although an earlier
report suggested that CD8+ was a feature of littoral cell angioma,  this has not been
and CD8 staining has been seen only in splenic hamartoma and some
Sclerosing angiomatous nodular transformation of the spleen is a benign
lesion of unknown histogenesis.
- Martel M, Cheuk W, Lombardi L, et al. Sclerosing angiomatoid nodular transformation (SANT): report of 25 cases of a distinctive benign splenic lesion. Am J Surg Pathol 2004;28:1268-79.
- Li L, Fisher DA, Stanek AE. Sclerosing angiomatoid nodular transformation (SANT) of the spleen: addition of a case with focal CD68 staining and distinctive CT features Am J Surg Pathol 2005;29:839-40
- Rosai J. Rosai and Ackerman's Surgical Pathology. 9th Edition. Edinburgh: Mosby, 2004:2035.
- Silverman ML, LiVolsi VA. Splenic hamartoma. Am J Clin Pathol 1978;70:224-9.
- Kaw YT, Duwaji MS, Knisley RE, et al. Hemangioendothelioma of the spleen. Arch Pathol Lab Med 1992;116:1079-82
- Rosso R, Chan JKC. Further evidence supporting the sinus lining cell nature of splenic littoral cell angiosarcoma Am J Surg Pathol 1996;20:1531.
- Ben-Izhak O, Bejar J, Ben-Eliezer S, Vlodavsky E. Splenic littoral cell hemangioendothelioma: a new low-grade variant of malignant littoral cell tumour Histopathology 2001;39:469-75.
- Arber DA, Strickler JG, Chen Y-Y, Weiss LM. Splenic vascular tumors: a histologic, immunophenotypic and virologic study. Am J Surg Pathol 1997;21:827-35.