RCC with rearrangement of ALK gene was first described by Debelenko et al. in 2011 [5]. Their report described a pediatric case with sickle cell trait, and the fusion partner of ALK gene was VCL gene. The first adult cases of ALK-RCC without a genetic background were reported in 2012 by Sugawara et al. [6]. They screened 355 RCC cases by ALK-IHC (using an intercalated antibody-enhanced polymer method) and identified two ALK-RCC cases which were confirmed to have TPM3-ALK and EML4-ALK fusion by fluorescence in situ hybridization assays.
Although ALK-RCC is extremely rare, its pathological features have been gradually revealed by the accumulation of case reports and studies [7]. ALK-RCC usually macroscopically presents a well- or ill-demarcated solid tumor, but cystic changes or a cystic lesion have also been reported [4, 8, 9]. The histological morphology of ALK-RCC is highly variable and heterogeneous, not only between cases, but also within individual cases [4]. Most ALK-RCC cases have exhibited mixed architectural patterns, including papillary, tubular, trabecular, tubulocystic, and solid patterns. The tumor cells typically showed eosinophilic cytoplasm and various degrees of mucin deposition [4, 7].
ALK-RCCs usually express PAX 8, CK7, and vimentin, and no specific IHC marker other than ALK-IHC has been reported [4]. It has been suggested that a strong membranous stain is characteristic of TPM3-ALK fusion [6], and our patient's case also showed strong membranous positivity for ALK-IHC, supporting that suggestion. The reported fusion partners to ALK gene include VCL, TPM3, EML4, HOOK1, and STRN gene [7]. Recently, PLEKHA7, CLIP1, KIF5B and KIAA1217 were reported as fusion partners of ALK gene [4, 10].
As described in the Introduction, the differential diagnosis of ALK-RCC varies widely, and ALK-RCC may mimic various renal tumors. As ALK-RCC may show mucin deposition and a tubular structure, the importance of the differential diagnosis of MTSCC has been noted [7]. However, to the best of our knowledge, no single case report of ALK-RCC that mimics MTSCC has been reported. Only one multi-institutional study of 12 cases described an ALK-RCC case morphologically resembling MTSCC which showed immunoreactivity compatible with MTSCC, i.e., positivity for PAX8, CK7, CD10, AMACR, and vimentin [4].
MTSCC is also a relatively rare epithelial neoplasm of low malignant potential with characteristic histologic features [11]. Although it was originally described as a tumor arising from cells of the loop of Henle or the collecting duct, the expression of CK7 and AMACR suggested its proximal nephron origin and its close resemblance to papillary RCC [12]. In the present case, although the findings of a lack of AMACR expression and lymph node metastasis were not typical findings of MTSCC, we initially considered MTSCC based on reports of rare cases of MTSCC that lacked AMACR expression, lymph node metastasis, and distant metastases [10, 13]. Considering the above-mentioned ALK-RCC case morphologically resembling MTSCC with AMACR expression, we strongly recommend an analysis of ALK expression by IHC when diagnosing a renal tumor that mimics MTSCC.
In conclusion, we have described a case of ALK-RCC which morphologically mimicked MTSCC. Since the use of molecular targeted therapy with an ALK inhibitor for cases of ALK-RCC is promising [6], the correct pathological diagnosis of ALK-RCC is quite important. In light of the lesson learned in the present case, we strongly recommend the routine performance of ALK-IHC in the pathological diagnosis of MTSCC.