Published online Feb 26, 2020. doi: 10.12998/wjcc.v8.i4.771
Peer-review started: October 20, 2019
First decision: December 4, 2019
Revised: December 11, 2019
Accepted: December 22, 2019
Article in press: December 22, 2019
Published online: February 26, 2020
Lymphoepithelioma-like carcinomas (LELC) are rare, malignant epithelial tumors that are generally considered a subtype of squamous cell carcinoma. LELCs are undifferentiated, with histological features bearing a striking morphological resemblance to non-keratinizing nasopharyngeal carcinomas. LELCs occur in multiple tissues across the body, including the salivary glands, thymus, lung, stomach, ovary, uterine cervix and breast. However, LELCs in the urinary tract are extremely rare, and to the best of our knowledge, most previously described urinary LELCs have been reported to occur in the bladder. Rationally speaking, there are likely to be distinctions between subtypes, related to the exact location, as well as specific risk factors associated with these carcinomas. This systematic review is an attempt to expand and synthesize findings to provide clinicians with guidelines for the best practices.
The limited current evidence is not sufficient to provide clinicians with clear guidelines, due to the relative rareness of these carcinomas. Even within the most common LELC locations, there remains some controversy. Several studies have identified an association between Epstein-Barr virus (EBV) and nasopharyngeal, stomach, and lung LELCs, although this association is not apparent in other locations. A previous systematic review of 142 patients diagnosed with bladder LELC, as well as several case reports focusing on renal LELCs, suggests that these types are not associated with the presence of EBV. There are several other controversies that should be investigated using meta-analytical techniques. Therefore, the general motivation was to differentiate all LELC types, and to identify risk factors for early identification, since little is known about upper urinary tract LELC (UUT-LELC).
The fundamental research objective of this study was to develop the evidence base for clinical diagnoses, and to engage patients in shared-decision making for the treatment of primary UUT-LELC.
A systematic search of PubMed, Embase, and other databases was conducted for all reports on UUT-LELC up until October, 2019, according to PRISMA guidelines. A database was then developed by extracting data from previously published reports in order to analyze interactions between clinical characteristics, pathological features, interventions and outcomes. Survival was analyzed using Kaplan–Meier estimates, which were compared using log rank tests.
A total of 28 previously published cases were identified for inclusion. The median age was 72 years with a male to female ratio of 4:3. Pure type LELCs were most common with 48.3% (n = 14), followed by 37.9% (n = 11) predominant LELCs and 3.4% (n = 1) focal LELCs. EBV testing was negative in all cases. Fourteen patients received radical nephroureterectomy (RNU)-based intervention. Twenty-three patients survived with no evidence of further metastasis. Six died before the median 18 mo follow-up point. Survival analysis suggests pure histological subtypes, and patients who receive complete tumor resection have more favorable prognoses. As always in cancer care, early identification generally increases the probability of interventional success.
Findings suggest that the treatment associated with the highest disease-free survival is an RNU-based intervention. However, this can only be a tentative recommendation given the limitations of this evidence base. We would encourage clinicians to actively communicate their findings and publish case reports. UUT-LELC cases may be rare, but there is an opportunity to save and prolong lives by sharing knowledge, enhancing the depth and breadth of data recording, and reporting and discussing clinical experiences.
Case reports are not generally high priority for publication houses, although a lot of very valuable information can be extracted and synthesized. This is an incredibly meaningful approach that we would encourage others to conduct, especially for rare conditions such as UUT-LELC. Clinicians must be guided by the best available evidence to reduce anxiety that may manifest through unnecessary testing and unclear guidelines. Systematic reviews of case reports and case series such as this one can also be used to support best practices, which will reduce the possibility of unnecessary harm.