Littoral cell neoplasm: A least understood splenic tumourK Ghosh
Fmr. Director: National Institute of Immunohaematology, KEM Hospital MS Building, Mumbai, Maharashtra, India
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/jpgm.jpgm_694_22
Source of Support: None, Conflict of Interest: None
I read with interest the report of a littoral cell angioma (LCA) of spleen detected after the patient was operated for renal cell carcinoma. Splenic tumor may evolve from lymphoid tissues, blood vessel/sinus endothelial cells, hemangioma, lymphangioma, its sarcomatous counterpart, Gaucher or other storage disease conditions, or hamartomas. However, LCA is a recently described benign neoplastic process with rare chances of becoming malignant.
The tumor was described in 1991 both by radiologists and by histopathologists/surgeons.,
So far less than 100 such cases have been described in world literature, and some series of cases also have been described with unusual association of various visceral, hematological malignancies and autoimmune disorders, e.g., colorectal carcinoma, pancreatic neuroendocrine tumor, renal cell cancer, hepatocellular carcinoma, non-small cell lung cancer, seminoma, ovarian cystadenocarcinoma, papillary thyroid cancer, transitional cell carcinoma of the bladder, pancreatic cystadenocarcinoma, myelodysplastic syndrome (MDS), and lymphomas to name a few.
Association of LCA with immunological disorders, such as ankylosing spondylitis, Crohn's disease, chronic glomerulonephritis, aplastic anemia, etc., has also been described.
Given the association of LCA with other malignancies as well as the few reported cases of its own malignant behavior, patients should undergo close follow-up after splenectomy., Guidelines for such follow-up needs to develop as we become more aware of its disease biology.
Renal cell carcinoma and visceral leiomyosarcoma have been described in association with LCA more often than others. In the present case under discussion, the elderly lady was first diagnosed with renal cell carcinoma which was operated. During follow-up, the splenic tumor and angiomyolipoma were detected in the contralateral kidney. This is a bit surprising as LCA is slow-growing tumor, and its, but unlikely, growth was missed during the work-up of renal cell carcinoma so also angiomyolipoma.
Angiomyolipoma as tumor (hamartoma) has been described with tuberous sclerosis complex, and both tuberous sclerosis 1 gene (TSC1) and tuberous sclerosis 2 gene (TSC2) have been linked to increased prevalence of renal cell carcinoma (RCC) in this disease. Hence, suspicion automatically arises whether in the present case renal cell carcinoma is a part of syndromic presentation of certain mutations as described below.
Several autosomal dominant inherited cancer syndromes predispose patients to clear cell and non-clear cell renal cell carcinoma. Among these are: i. von Hippel–Lindau disease (VHL), ii. hereditary leiomyomatosis and RCC (HLRCC), iii. hereditary papillary RCC, and iv. Birt–Hogg–Dubé syndrome, caused by germline mutations.
Syndromic and congenital mutation leading to renal cell carcinoma occurs at much earlier age than the present case. So LCA and hypernephroma association has to be explained by other means which at present remains elusive.
LCA has been associated with different peripheral cytopenias and hypersplenism too. The histopathology and electron microscopy along with immunophenotyping have shown that this tumor co-expresses both endothelial and histiocytic antigens. Electron microscopy also showed histiocytic and endothelial nature of the tumor cells. These cells are generally CD34 negative and have very low Ki-67 antigen staining, providing the basis for slow-growing nature of this tumor.,
Papillary fronds of this tumor floats in the red pulp of the spleen and may cause hypersplenism. The tumor is CD21, CD31, CD68, and CD163 antigen positive as well as it is also positive for von Willebrand antigen but negative for CD8 and CD4 antigens.
Formin homology domain-1 antigen expression is characteristic for the tumor; occasionally, S-100 antigen is also expressed. Various imaging modalities have not shown any characteristic diagnostic feature for the tumour and spontaneous rupture of spleen as well as myeloid metaplasia has been reported along with multitude other conditions already described.
LCA is a rare neoplasm of spleen, mostly is of low-grade nature. Splenectomy is curative in most cases. The condition is associated with multitude of malignant, non-malignant tumors, hematologic/immunologic conditions which may precede, follow, or present simultaneously with this neoplasm. Detection of this condition mandates extensive search and regular follow-up of patients indefinitely for existence and development of visceral malignancies, other autoimmune and hematologic disorders. Ultimate pathobiologic mystery—why this tumor be associated with so many malignant or non-malignant conditions—is as yet unknown and needs further studies.