Renal haemangioblastoma (RHB) is extremely uncommon since only four cases were definitely reported previously (Table ). Our case was specifically in line with the diagnostic clues of RHB suggested by Ip et al [5
] and Verine et al [6
]. Those characteristics included circumscribed borders, paucity of mitotic figures, fine vacuoles in some tumor cells indicating presence of intracytoplasmic lipids, and a rich capillary network. The immunoprofiles (S100 +, NSE+, a-inhibin + and AE1/AE3-) also conformed to those of haemangioblastomas. However, the majority of the tumor cells in our case showed rhabdoid features, which may be easily mistaken for other rhabdoid tumors that are known to occur in the kidney.
Clinicopathological characteristics of the reported sporadic hemangioblastomas in the kidney
In our opinion, the first differential consideration is the malignant rhabdoid tumors (MRTs). Although most of MRTs afflict young children, there still are sporadic cases affecting adults [7
]. Several features seen in our case do not support the diagnosis of MRTs: (i) MRTs generally show vesicular chromatin, prominent nucleoli and hyaline intracytoplasmic inclusion [8
]. The neoplastic cells in our case demonstrated dark-stained and coarse granular chromatin, and lack the discernable nucleoli as well as cytoplasmic inclusions. (ii) MRTs are devoid of the cytoplasmic lipid droplets and arborizing stromal vasculature, characterized by haemangioblastomas. (iii) Immunohistochemically, MRTs occasionally are focally positive for S100 and NSE [9
], but a-inhibin staining was not shown. The features are different from the extensive expression of S100, NSE and a-inhibin seen in RHB. (IV) MRTs are a highly invasive and lethal neoplasm with a proliferation index of Ki-67 around 95% [8
]. In contrast, the extremely low Ki-67 index and rare mitosis indicate an indolent behavior of our case.
Another necessary differential consideration is renal cell carcinomas with rhabdoid features (RCCR), which have been previously described [10
]. RCCR are predominantly composed of large polygonal cells with eccentric nuclei and eosinophilic cytoplasm. Of the 23 cases analyzed by Gökden et al. [10
], RCCR showed a diffuse NSE staining (79% of cases) and focal positive staining for EMA (47% of cases) and S-100 (37% of cases), whereas cytokeratin expression was decreased (56% of cases). Obviously, there are many morphologic and immunophenotypic features that markedly overlap with our present case. Nevertheless, compared with RCCR, the tumor cells of our case did not display the vesicular nuclei and prominent nucleoli. Furthermore, RHB is characterized by abundant vascular networks, which are strikingly reduced in RCCR [11
]. In addition, RHB demonstrates negative PAS staining for glycogen, whereas this staining is positive in RCCR [11
]. The low Ki-67 index in our case is also not compatible with the high proliferative index in RCCR [12
Other neoplasms with rhabdoid features possibly that need to be considered before making the diagnosis of RHB include epithelioid angiomyolipoma (HMB-45+
), malignant melanoma with rhabdoid features (HMB-45+
], paraganglioma (synaptophysin+
), epithelioid leiomyosarcoma with rhabdoid features (SMA+
], and epithelioid malignant peripheral nerve sheath tumor (a-inhibin-
Interestingly, focal CD10 positivity was observed in some tumor cells of our present case. In the normal kidney, CD10 stains glomerular cells and proximal convoluted tubules, and participates in the regulation of water and sodium metabolism [16
]. Thus, CD10 expression in RHB seemingly substantiates the earlier hypothesis that haemangioblastomas are derived from pluripotent mesenchymal cells, and partially acquire some site-specific markers of their parental organs during pathogenesis [4
]. Many studies have suggested CD10 is a powerful marker in the differentiation between renal cell carcinoma and haemangioblastoma since it usually demonstrates positive staining in renal cell carcinoma while is steadily negative in haemangioblastoma [17
]. Our result indicates that caution should be taken on evaluating the differential efficacy of this reagent. Noticeably, Verine et al. [6
] reported a negative result of CD10 staining in their case of RHB. The reasons for the discrepancy remain unknown, and probably either reflect the intrinsic disparities of expressional profiles between the two specimens, or may be just caused by different antibodies used.
Some investigators have suggested that RHB would not be as rare if it had got wider recognition as a primary renal tumor [5
]. So it is undoubtedly necessary to be aware of the clinicopathologic characteristics of RHB. From the available data, RHB commonly occurs in the elderly people (range 55 to 71 years) and there is no sex predilection. The right kidney seems more prone to be affected and the superior pole is likely the preferential site of mass development. Grossly, these tumors displayed a solid cut surface, though cystic changes were occasionally observed. Architecturally, the lesions were consistently composed of cellular and paucicellular regions. In the cellular areas, the tumor could be subclassified as reticular and cellular variants analogous to cerebellar haemangioblastoma [18
]. In the paucicellular zones, stromal fibrosis was prominent. Cytologically, the neoplastic cells in RHB generally contained mild to remarkably eosinophilic cytoplasm and frequently outnumbered the clear cells with rich lipid droplets. The nuclei were often enlarged and hyperchromatic, and frequently displayed some pleomorphism. In addition to the positivity for S100, a-inhibin and NSE, focal expression of EMA, SMA, MSA and calponin were also noted [5
]. Nevertheless, Cytokeratins, HMB-45, Melan-A, chromogranin, calretinin, and Myoglobin were characteristically negative.
Compared with cerebellar haemangioblastoma (CHB), RHB manifest with some different features. For instance, RHB incidence peaks in the sixth decade compared to the fourth decade of CHB [19
]. RHB usually presents as a solid mass, whereas 65 percent of CHB manifest as a cystic mass [20
]. The acidophilic cytoplasm and pleomorphic nuclei that are frequently present in renal tumors are usually not seen in CHB. Stromal hyalinization in RHB is also more prominent than that in CHB. However, the immunophenotype and benign behaviors of RHB reflect the essential consistency with CHB.