CASE REPORT
Synchronous occurrence of littoral cell angioma and multiple primary malignancies - A rare case report
Jaseela Teeka, Shahin Hameed, Shalini Kuruvilla, Karthika Kundil Veetil Department of Pathology, Aster MIMS, Calicut, Kozhikode, Kerala, India
Address for correspondence: Dr. Jaseela Teeka, Department of Pathology, Aster MIMS, Calicut, Govindapuram (Po), Kozhikode, Kerala, India. E-mail: jaseelaalkhaf@gmail.com
ABSTRACT
Littoral cell angioma (LCA) is a rare primary vascular neoplasm of the spleen that originates from the endothelial littoral cell lining of the red pulp sinuses. LCA has mostly benign behavior with a few reported cases of malignancy. LCA is strongly associated with diverse immunologic and neoplastic disorders. We report a case of LCA with synchronous renal cell carcinoma, adrenal cortical adenoma and JAK2 EXON 14 mutation positive Polycythemia vera. Histologically, entire spleen showed a neoplasm with anastomosing vascular channels lined by plump round cells. Diagnosis was confirmed by the endothelial/histiocytic phenotype of tumor. To the best of our knowledge, this case is the first description of LCA associated with renal cell carcinoma, adrenal cortical adenoma and MPN.
KEY WORDS: Adrenal cortical adenoma, JAK 2 mutation, littoral cell angioma, polycythemia vera, renal cell carcinoma
INTRODUCTION
Littoral cell angioma (LCA) is a rare, primary splenic hemangioma, accounting for only about 1% of all splenic neoplasm. It is a vascular neoplasm, arise from endothelial lining of splenic red pulp sinuses. It has a distinctive phenotype with mixed endothelial/histiocytic differentiation.[1] Both benign and malignant cases have been reported. Etiology is un known, but a role of immune dysregulation is suggested since it is associated with other malignancies and inflammatory condition.[2] Here we present a case of 49-year-old man presented with obstructive jaundice found to have multiple tumors including littoral cell angioma, clear cell renal cell carcinoma, adrenal cortical adenoma and JAK2 mutation positive polycythemia vera.
CASE PRESENTATION
For 3 months, a 49-year-old man with Type 2 diabetes mellitus and hypertension had symptoms of nausea, disturbed sleep patterns, weight loss, and appetite reduction. He experienced 2 months of high-colored urine and a 16-kg weight loss. He had a history of using complementary and alternative medicine (CAM) and had yellowish discoloration of eyes. Upon examination, he had significant hepatosplenomegaly [Figure 1a] and icterus. His blood investigation showed elevated lactose dehydrogenase (253 U/L) total bilirubin (10.7 mg/dl), direct bilirubin (8.3 mg/dl) and Prothrombin time (18 sec). CT Abdomen performed with the impression of cholestatic jaundice revealed a right kidney lesion [Figure 1c] that was heterogeneously enhancing, along with left adrenal lesion [Figure 1b]. A provisional diagnosis of Renal cell carcinoma with adrenal metastasis was considered. Right radical nephrectomy with left adrenalectomy was performed. Per-operative unintentional splenic trauma resulting in excessive bleeding ended up in splenectomy [Figure 2b]. In view of co-existing myeloproliferativeneoplasm (MPN)/
Access this article online
Website: https://journals.lww.com/ijpm
DOI: 10.4103/ijpm.ijpm_603_24
Quick Response Code:
Stauffer’s syndrome, a liver biopsy and marrow biopsy for JAK2 exon 11 mutation studies were also done. Histopathology from the kidney mass and adrenal lesion turned out to be Clear cell renal cell carcinoma [Figure 2a and Figure 3d-f] and an adrenocortical adenoma [Figure 2c and Figure 3g-j], respectively. Surprisingly the spleen showed features of Littoral cell angioma [Figure 3a-c]. The liver biopsy showed cholestasis [Figure 3k] whereas the
Submitted: 18-Jul-2024 Revised: 19-Nov-2024 Accepted: 11-Feb-2025 Published: 07-Jun-2025
This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License (CC BY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
For reprints contact: WKHLRPMedknow reprints@wolterskluwer.com
How to cite this article: Teeka J, Hameed S, Kuruvilla S, Veetil KK. Synchronous occurrence of littoral cell angioma and multiple primary malignancies - A rare case report. Indian J Pathol Microbiol 2025;68:858-61.
858
marrow showed features of MPN [Figure 3l] and positive JAK2 exon 14 mutation studies clinched a diagnosis of Polycythemia Vera.
DISCUSSION
Littoral cell angioma is rare benign, indolent splenic neoplasm with dual endothelial and histiocytic differentiation arising from sinus lining of red pulp. There is no age or gender predilection, but most of the cases have affected middle aged adults. It can be associated with internal malignancies and thus can mimic metastatic disease radiologically.
a
b
c
50% of the cases are asymptomatic. These are usually detected in incidentally by imaging or in splenectomy specimens performed for unrelated etiology. Some cases have been presented with fever, pain abdomen, weight loss and cytopenia’s associated with hypersplenism. 40%-60% cases are found to be associated with malignancies of epithelial, mesenchymal, and hematological origin.[3]
LCA was first described by Falk et al. in 1991.[4] The vascular tumors of spleen include hamartoma, hemangioma, lymphangioma, hemangioendothelioma, angiosarcoma, LCA, and sclerosing angiomatoid nodular tumors.
Lymphoma, myelodysplastic syndrome, and aplastic anemia are also quite common in the LCA patients.[5] In a retrospective case study conducted in 17 cases of LCA, Bi et al.[6] found that LCA was associated with congenital and immunological disorders like ankylosing spondylitis, aplastic anemia, myelodysplastic syndrome, chronic glomerulonephritis, Gaucher disease, Crohn’s disease, Wiskott-Aldrich syndrome, lymphocytic colitis and Epstein syndrome.
The usually associated organ malignancies include cancers of lung, kidney, pancreas, colon, and ovary. The definite pathogenic mechanism of this association has not been known so far. The atraumatic splenic ruptures are thought to be related to underlying infection or hematologic malignancy.[7]
Imaging modalities are nonspecific for diagnosis of littoral cell angioma. They could appear as diverse echoes on ultrasound, and different densities and signals on CT and MRI with a delayed enhancement generally.[8]
Histology shows proliferation of anastomosing, tortuous, blood-filled vascular channels with irregular lumina, papillary projections and cystic spaces. These are lined by endothelial cells with variable hemophagocytosis.
The immunohistochemical staining for littoral cells usually reveals a dual differentiation pattern for both endothelial and histiocytic markers. The histiocytic markers positive include CD163, CD68, lysozyme, CD4, and CD11c and the vascular markers positive include CD31, FLI1, LYVE1, VEGFR2, claudin-5, and LMO2. As a tumor suppressor gene, Wilmstumor-1 (WT-1)
a
b
c
a
b
c
0
R
d
e
f
g
h
i
j
k
l
played a role in regulating angiogenesis and proliferation of vascular smooth muscle cells. But usually WT1, CD34 and ERG are found to be negative.
Currently, standard treatment of LCA is open splenectomy or hand-assisted laparoscopic total splenectomy.[9] Recent studies showed that the majority of LCA patients who underwent splenectomy were at the risk of long-term complications, such as sepsis, thrombus, and tumor metastasis. Recently, TNF-& has been suggested to have a role in the pathogenesis of LCA. LCA may rarely present with thrombocytosis instead of thrombocytopenia; and may possibly be associated with splenic infarction and hematologic malignancies.[10]
CONCLUSION
Littoral cell angioma (LCA) is a rare benign tumor. Both benign and malignant cases have been reported. It is thought to be arising from red sinus shore cells of the reticuloendothelial system in the spleen. There are case reports describing the association of cancers of lung, kidney, colon, pancreas, and ovary with LCA. So far six cases have been reported for Littoral cell angioma associated with renal cell carcinoma. This report is the 7th known description of LCA associated with renal cell carcinoma No cases have been reported with association of littoral cell angioma, adrenal cortical adenoma and myeloproliferative neoplasms. So, this is the first
case showing synchronous tumors of littoral cell angioma, clear cell renal cell carcinoma, adrenal cortical adenoma, polycythemia vera with JAK2 Exon 14 mutation. Whether the JAK 2 mutation have any association with pathogenesis of LCA is unknown.
Take home message
Close follow-up and careful investigation in search of multiple visceral neoplasm are strongly recommended in cases of LCA, but further clinical observations and more in-depth genetic and molecular studies are needed before any valid conclusions can be drawn.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
REFERENCES
1. Liu D, Chen Z, Wang T, Zhang B, Zhou H, Li Q, et al. Littoral-cell angioma of the spleen: A case report. Cancer Biol Med J 2017;14:194-5.
2. Hansen T, Habekost M, Flieger D, Kirkpatrick CJ. Littoral cell angioma of the spleen. Association with colon and hepatocellular carcinoma. Pathologe J 2010;31:290-2.
3. Rai M, Gupta N. Littoral Cell Splenic Angioma. StatPearls; 2023.
4. Falk S, Stutte HJ, Frizzera G. Littoral cell angioma: A novel splenic vascular lesion demonstrating histiocytic differentiation. Am J Surg Pathol 1991;15:1023-33.
5. Shen H, Zhu Y, Zhong J, Shen Y, Huang Y, Song P, et al. Littoral cell angioma of the spleen: A study of 10 cases case series and literature review. Medicine (Baltimore) 2024;103:e37550.
6. Bi CF, Jiang LL, Li Z, Liu WP. Littoral cell angioma of spleen: A clinicopathologic study of 17 cases. Zhonghua Bing Li Xue Za Zhi 2007;36:239-43.
7. Bisceglia M, Sickel JZ, Giangaspero F, Gomes V, Amini M, Michal M, et al. Littoral cell angioma of the spleen: An additional report of four cases with emphasis on the association with visceral organ cancers. Tumori 1998;84:595-9.
8. Wang W, Qi G, Zhao X, Zhang Y, Zhu R, Liang R, et al. Clinical Landscape of Littoral Cell Angioma in the Spleen Based on a Comprehensive Analysis. Front Oncol 2022;12:790332.
9. Moore RF, Sholl AB. Case Report Littoral cell angioma associated with extramedullary hematopoiesis and renal cell carcinoma: Case report and review. Int J Clin Exp Pathol 2016;9:6610-6.
10. Ozer N, Sozutek A, et al. Littoral cell angioma of the spleen presenting with thrombocytosis and splenic infarct. J Coll Physicians Surg Pak 2021;31:986-8.