Splenic surprise in a case of renal cell carcinoma: Unusual case or association?T Agrawal1, S Epari1, G Prakash2, S Menon1
1 Department of Pathology, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, Maharashtra, India
2 Department of Urology, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, Maharashtra, India
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/jpgm.jpgm_285_22
Source of Support: None, Conflict of Interest: None
Keywords: Littoral cell angioma, red pulp, renal cell carcinoma, spleen
Splenic tumors are rare neoplasms. Littoral cell angioma (LCA), a rare vascular tumor, is one of the benign mesenchymal tumors of the spleen arising from the lining cells of the venous sinuses of the red pulp. These tumors do not have a soft tissue counterpart. The littoral cells are distinctive endothelial cells with partial histiocytic function, as asserted by their hybrid endothelial/histiocytic phenotype on immunohistochemistry. A proportion of cases are associated with internal malignancies.,
We present a rare case of LCA of the spleen in a patient suspected to have metastatic renal cell carcinoma (RCC).
A 61 years-old female, known hypothyroid on medication and previously operated for a left breast benign phyllodes tumor in 2015, was incidentally detected in the follow-up period with a right renal mass on a triple-phase computed tomography (CT) abdomen in 2017. A 39 × 37 mm flurodeoxyglucose (FDG) avid soft tissue mass was seen involving the upper pole of the right kidney (standardized uptake values (SUV) max: 7.23). No FDG avid lymphadenopathy or bony lesions were seen. Right partial nephrectomy confirmed a clear cell renal cell carcinoma (CCRCC), International Society of Urological Pathology (ISUP) grade II (Stage T1bNx). The patient was on regular follow-up and disease free till December 2020 when she was found to have a stable 11 × 11 mm hyperechoic lesion in the lower pole of the left (contralateral) kidney, radiologically suggestive of angiomyolipoma. There was no history of epilepsy or other lesions, including skin changes to suggest the possibility of tuberous sclerosis. In June 2021, a contrast-enhanced computed tomography (CECT) abdomen scan detected a 23 × 20 mm splenic mass lesion, which was suspicious of metastasis. The peripheral blood counts were in the normal range. The patient underwent laparoscopic splenectomy. Grossly, the splenic capsule was unremarkable. On the cut surface, a single 3 × 2.5 × 2 cm firm, gray-white circumscribed lesion was identified in the splenic parenchyma [Figure 1]a. Histologically, the lesion was well circumscribed and showed numerous proliferating, anastomosing, and tortuous vascular channels lined by cells with plump spindle-shaped nuclei, having vesicular chromatin, inconspicuous nucleoli, and a moderate amount of amphophilic cytoplasm [Figure 1]b and [Figure 1]c. Mitosis and necrosis were not seen. Scattered admixed inflammatory cells comprising lymphocytes, eosinophils, and histiocytes, were also identified. Normal red and white pulp was not seen within the lesion. On immunohistochemistry, the tumor cells were immunoreactive for cluster of differentiation (CD) 31 [Figure 1]d, CD68, CD163 [Figure 1]e, and CD4 [Figure 1]f; while being negative for CD34, CD8 [Figure 1]g, S100p, c-kit, TFE3 transcription factor binding to IGHM enhancer 3, and cytokeratin (AE1/AE3). Hence, the lesion was diagnosed as LCA.
The patient is on regular follow-up post-splenectomy and has been vaccinated as per standard practices.
Primary mass lesions of the spleen are rare. More frequently, the spleen is involved by hematogenous metastases from primary breast carcinoma, bronchogenic carcinoma, malignant melanoma, gastric carcinoma, pancreatic carcinoma, and colorectal carcinoma. Primary vascular tumors of the spleen are a further uncommon group of lesions. LCA is one such tumor and was first identified in 1991 by Falk et al. It is unique owing to its origin from the sinus lining cells in the red pulp and thus does not have a soft tissue counterpart. Other vascular tumors of the spleen, which can morphologically mimic LCA, include hamartoma, hemangioma, lymphangioma, hemangioendothelioma, angiosarcoma, and sclerosing angiomatoid nodular tumor (SANT). These can be differentiated from LCA by the absence of co-expression of histiocytic markers on the endothelial cells. Additionally, the cellular atypia seen in cases of hemangioendothelioma and angiosarcoma is not seen with LCA. Mitosis is very occasional or absent and the Ki-67 labeling index is low in cases of LCA.
Most LCAs are clinically latent. These are usually detected incidentally by imaging or in splenectomy specimens done for an unrelated etiology. There is no age or gender predilection.
LCA inherits the dual phenotype of endothelial and histiocyte origin, from that of normal sinus lining endothelium of red pulp from which it originates. Thus, immunohistochemically it expresses histiocytic markers (i.e., CD68, CD163, CD4, lysozyme) and endothelial markers (i.e., CD31). However, the tumor cells do not express CD34 and CD8 (positive in normal sinus lining cells), thus differentiating LCA from the normal splenic red pulp. The current case had all classical histological features and immunoprofile of LCA. The preoperative CECT scan, however, showed a contrast-enhancing splenic mass, which was suggestive of metastasis from the previously diagnosed RCC.
LCA is associated with other malignancies, including epithelial, mesenchymal, and also hematological malignancies. Bisceglia et al. reported four cases of LCA associated with other malignancies, and pointed out the striking association of LCA with visceral organ cancers. Only one case in their series had an associated RCC. This observation was supported by subsequent studies, as approximately a third of LCAs reported to date have been found to accompany an internal malignant neoplasm. In a study by Peckova et al., 15/25 patients with LCA had an associated visceral malignancy, including colorectal carcinoma (5 cases), RCC (3 cases), endometrial adenocarcinoma (1), pancreatic adenocarcinoma (1), prostatic adenocarcinoma (1), gastrointestinal stromal tumor of the stomach (1), carcinoma of the thyroid gland (1), breast cancer (1), and melanoma (1). All associated renal carcinomas were conventional RCC.
The radiological suspicion of angiomyolipoma in the contralateral kidney raises suspicion for tuberous sclerosis. In one study, the renal carcinomas associated with this syndrome were classified as “TSC-associated papillary RCC,” “hybrid oncocytic chromophobe tumor,” and “unclassifiable with eosinophilic cytoplasm”; and occurred at a mean age of 30 years. CCRCC was not identified. LCA has not been seen to be associated with this syndrome.
The co-occurrence of LCA in this diagnosed case of CCRCC was a surprise finding. Radiologically, the lesion mimicked metastasis and a non-surgical approach to management would have labeled this patient as having a metastatic RCC. Awareness of this rare co-occurrence can enable appropriate management decisions.
To conclude, LCA is a rare, indolent splenic benign vascular lesion with dual endothelial and histiocytic phenotype arising from sinus lining cells of the red pulp. It can be associated with internal malignancies and thus can mimic metastatic disease radiologically. Awareness of this rare association should be borne in mind.
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