T Morikawa, T Toyoshima, M Fukayama
epstein-barr virus, immunohistochemistry, in situ hybridization, lymphoepithelioma-like carcinoma, ureter
T Morikawa, T Toyoshima, M Fukayama. Lymphoepithelioma-like carcinoma of the ureter. The Internet Journal of Pathology. 2008 Volume 9 Number 2.
We report an extremely rare case of lymphoepithelioma-like carcinoma of the ureter. A 73-year-old man presented with asymptomatic gross hematuria. Based on the clinical diagnosis of a left ureteral tumor, the patient underwent left nephroureterectomy. Histological examination showed lymphoepithelioma-like carcinoma of the ureter with a unique growth pattern of submucosal spread, in which cytokeratin immunohistochemistry clearly demonstrated the cluster of neoplastic cells within the dense lymphocytic infiltrates. The tumor cells showed negative results for the presence of Epstein-Barr virus by Epstein-Barr virus-encoded ribonucleic acid
Lymphoepithelioma is an undifferentiated carcinoma with intense lymphoid infiltrates arising in the nasopharynx. 1 Carcinomas that histologically resemble lymphoepithelioma of the nasopharynx are called lymphoepithelioma-like carcinoma (LELC). Only five patients with LELC of the ureter have been reported in English literature previously 23456 . Here, we report an additional case of LELC of the ureter which showed a unique spreading lesion, and discuss about potential diagnostic pitfalls for this rare type of ureteral carcinoma, LELC.
A 73-year-old man presented with asymptomatic gross hematuria. Retrograde pyelography revealed a defect in the upper ureter. Magnetic resonance imaging showed a mass in the left upper ureter that measured about 2 cm in its greatest dimension. Based on the clinical diagnosis of a left ureteral tumor, the patient underwent left nephroureterectomy.
Macroscopically, a solid tumor measuring 2.2×1.8 cm was protruding into the dilated upper ureteral lumen near the ureteropelvic junction (Fig 1). The distal ureteral wall was thickened for 1.6 cm in length, continuously with the solid tumor.
Microscopically, the tumor consisted of invasive nests of large undifferentiated cells in a dense lymphoid stroma (Figures 2 and 3). In the region of the solid tumor, neoplastic cells were admixed with lymphoid infiltrates and grow expandingly into the deep muscularis propria of the ureter (Fig 2). Tumor cells had large vesicular nuclei and prominent nucleoli with indistinct cytoplasmic membranes, which formed syncytium-like nests (Fig 3, inset). In the region of ureteral wall-thickening, the surface was covered with non-neoplastic urothelium, and there were massive lymphoid infiltrates in the lamina propria (Fig 3). Higher magnification demonstrated scattered small tumor nests within the infiltrates (Fig 3, inset), which might provide an impression of aggregates of macrophages or abortive germinal center. There was no component of conventional urothelial carcinoma, neither flat nor papillary type.
Immunohistochemically, tumor cells were strongly positive for cytokeratin AE1/AE3, which confirmed their epithelial origin (Figure 4). The stromal lymphoid cells showed a predominance of CD3-positive T cells compared to CD20-positive B cells, mixed with a small number of plasma cells and eosinocytes.
Pathological diagnosis was LELC of the left ureter, pT2b N0. Neither lymphatic vessel nor blood vessel invasion was identified. Surgical margins were negative. Postoperatively, no adjuvant therapy was performed. The patient was free of tumor recurrence and metastasis 15 months after the operation.
LELC has been described in various organs including the stomach, salivary glands, lung, thymus and urinary tract. LELC of the upper urinary tract remains extremely rare. Only five and seven patients, respectively, with LELC of the ureter 23456 and renal pelvis 7 have been reported in English literature previously.
Most patients with LELC of the ureter present with asymptomatic gross hematuria 2456 . Histologically, LELC is characterized by syncytium-like nests of undifferentiated carcinoma associated with a prominent lymphoid infiltrate. Our case showed typical histological findings of LELC. However, the growth pattern of ureteral submucosal spread was unique to this case (Figure 3), which has not been previously reported. Since LELC can be present as a submucosal tumor covered by non-neoplastic epithelium, LELC of the urinary tract can be misdiagnosed as chronic inflammation, especially when only small specimens (i.e., ureteroscopic biopsy specimens) are available for the diagnosis. Appropriate sampling and careful observation with immunohistochemistry for cytokeratins are necessary for correct diagnosis.
EBV infection is closely associated with lymphoepithelioma of the nasopharynx and LELC of some organs 8 . Concerning LELC of the urinary tract, however, no reported case has shown any association of EBV, as in our case 17 . Despite the morphological similarity to lymphoepithelioma of the nasopharynx, there may be an alternative etiology for LELC in the urinary tract, such as an exaggerated host immune response.
It has been proposed that LELC of the urinary tract has a relatively favorable prognosis in pure or predominant forms 9 . Concerning LELC of the ureter, all the five previously reported cases showed no evidence of disease after surgical resection 23456 . Expanding rather than infiltrative growth pattern, (Figure 2), absence of lymphovascular invasion, and complete resection of the tumor suggested a favorable prognosis in our case. However, the follow-up period of the reported cases was relatively short (range 12 to 30 months). Moreover, contrary to previous reports, a recent study by Tamas
In conclusion, we reported a case of LELC of the ureter. Recognition of this type of tumor is important to avoid misdiagnosis.
We are grateful to Kei Sakuma and members of department of pathology, Yuai Memorial Hospital, for excellent technical support.