Kohei Shomori md phd, Division of Organ Pathology, Department of Microbiology and Pathology, Faculty of Medicine, Tottori University, 86, Nishi-cho, Yonago, Tottori 683-8503, Japan. Email: firstname.lastname@example.org
Abstract: Patients receiving long-term hemodialysis tend to develop renal cell carcinoma (RCC). Among such cases, chromophobe RCC and so-called ‘capsulomas’ are rarely reported. Here, we report a case of a Japanese woman in her early 70s, who developed both renal lesions after 17 years of hemodialysis. The patient received radical nephrectomy for enlarging renal mass. Grossly, the resected kidney showed a dominant tumor and small-sized subcapsular nodules. Histologically, two types of neoplasm, chromophobe RCC and ‘capsuloma’, existed with acquired cystic disease of the kidney. Chromophobe RCC had eosinophilic cytoplasm with perinuclear halos, and some tumor cells showed oncocytic features. Hale's colloidal iron staining showed a weakly positive cytoplasmic reaction. Immunohistochemistry was diffusely positive for cytokeratin 7, but negative for vimentin in the tumor cells. ‘Capsulomas’ were multiple subcapsular nodules composed almost entirely of smooth muscle-like cells with immunoreactivity for melanosome-associated antigen detected by HMB-45.
It is well known that the incidence of renal cell carcinoma (RCC) is 14–17-fold higher in hemodialysis patients than in the rest of the population.1,2 Ishikawa has reported that the incidence of the chromophobe type is less than 2% in patients treated with hemodialysis.1 Compared with the general population (almost 5% of total RCC), chromophobe RCC in hemodialysis patients is rare.3,4
Angiomyolipoma (AML) is a benign mesenchymal tumor composed of variable proportions of adipose tissue, spindle and epithelioid smooth muscle cells (SMC), and abnormally thick-walled blood vessels. AML accounts for ∼1% of surgically removed renal tumors.5 Subcapsular small-sized AML has been referred to as ‘capsuloma’, which is composed almost entirely of SMC mimicking leiomyoma.6–8
Here, we report a rare case with two types of renal tumor, chromophobe RCC and ‘capsuloma’, in a patient with acquired cystic disease of the kidney (ACDK) undergoing long-term hemodialysis.
A Japanese woman in her early 70s had received hemodialysis for 17 years for chronic renal failure caused by glomerulonephritis. She underwent abdominal computed tomography (CT) for periodical systemic screening. Abdominal CT scanning showed multiple cysts in both kidneys and a homogeneous tumor in the left kidney, which was compatible with RCC (Fig. 1). CT did not reveal either tumor vein thrombus or hilar nodal metastasis. The patient underwent left radical nephrectomy under general anesthesia for the treatment of RCC. Pre-hemodialysis laboratory data on admission showed high serum levels of creatinine and renal anemia. The patient had no symptoms associated with the renal tumor, and no remarkable past medical history. No sign of tuberous sclerosis was noted. The postoperative course was uneventful and the general condition of the patient is good, 1 ;year after the operation.
Two types of tumor (one dominant and several small nodules) were observed grossly in the resected kidney (Fig. 2A). One was solid, well-circumscribed, and measured 2 cm in diameter. The cut surface was homogeneous, and whitish gray in color, without necrotic changes. The others were situated in the subcapsular region. They were relatively well-circumscribed and were not noticed by preoperative CT. They were gray in color, and measured less than 1 cm in diameter.
Histologically, the dominant tumor showed expansive proliferation and was well demarcated from the surrounding tissue (Fig. 2B). The tumor was composed of large polygonal cells arranged in solid sheets, without necrosis and hyalinization. Tumor cells possessed weakly eosinophilic and cloudy cytoplasm, with prominent cell membranes and perinuclear halos (Fig. 3A). The cells had irregular-shaped nuclei, often wrinkled, with a few showing binucleation. Mitoses were rare. A small population of tumor cells possessed eosinophilic and granular cytoplasm and indistinct cell borders with round nuclei. The tumor had mostly hyalinized collagenous stroma separating the cell sheets with capillaries. Tumor cells showed diffuse but weak cytoplasmic staining upon Hale's colloidal iron staining (Fig. 3B). Thus, the tumor was diagnosed as an eosinophilic variant of chromophobe RCC. On immunohistochemical examination, chromophobe RCC was diffusely positive for pan-cytokeratin (AE1/3, 1:50; DAKO, Glostrup, Denmark), epithelial membrane antigen (EMA) (prediluted; Nichirei, Tokyo, Japan), cytokeratin (CK) 7 (1:50; DAKO) and CK8 (1:50; DAKO), and negative for CK20 (1:50; DAKO), CD10 (prediluted; Nichirei), vimentin (prediluted; Nichirei), á-smooth muscle actin (SMA; 1:50; DAKO), S-100 protein (1:50; Nichirei), and CD117/c-KIT (1:100; DAKO). The Ki-67 (1:50; DAKO) index was <1%.
Multiple subcapsular nodules were composed of entangled eosinophilic spindle cells (Fig. 2B). Tumor nodules had slit-like blood vessel components. A few trapped tubules were intermingled in the nodules. The tumor cells were composed predominantly of eosinophilic, spindle-shaped, SMC-like cells (Fig. 4A). A few tumor cells showed clear cytoplasm, and others had cloudy eosinophilic cytoplasm. The tumor cells possessed oval nuclei without mitotic figures. There was no adipose tissue in the nodules. Tumor cells were diffusely positive for SMA, desmin (1:50; DAKO), vimentin, HMB-45 (1:50; DAKO; Fig. 4B) and CD117/c-KIT, but negative for CD34, AE1/3, EMA and S-100 protein. These findings were consistent with so-called ‘capsulomas’.
We present a case of an eosinophilic variant of chromophobe RCC and ‘capsulomas’ in a patient with ACDK.
The patient had received hemodialysis for 17 years, and chromophobe RCC had indisputably occurred from ACDK. The incidence of RCC in hemodialysis patients is 10-fold higher than that in the rest of the population. Ishikawa has reviewed 403 cases of RCC in hemodialysis patients, and has reported that the incidences of clear cell, granular, chromophobe and spindle cell types are 55.1, 17.4, 2.0 and 3.0%, respectively.1 Although this result should be reevaluated based on the current histological classification, i.e. granular subtype, the incidence of chromophobe RCC is almost one tenth of that in the general population. Tickoo et al. have reviewed 66 end-stage renal disease affected kidneys and reported that the incidence of clear cell, papillary and chromophobe types is 18, 15 and 8%, respectively.9 Kojima et al. have also reviewed 44 RCC that occurred from end-stage renal disease kidneys and reported that the incidence of chromophobe RCC is 8.2%.2 These results were similar to those seen in sporadic cases. Considering the number and race of the patients studied, Ishikawa's results should be more reliable at least concerning the Japanese; chromophobe RCC in hemodialysis patients is rare.
On the other hand, subcapsular small nodules were classified as ‘capsulomas’: small-sized subcapsular AML, because of their predominantly eosinophilic, spindle-shaped SMC-like cells, without adipose cells, and immunoreactivity for HMB-45. AML is composed of three heterogeneous components of blood vessels, SMC-like cells and adipose cells. The proportion of the three tissue components varies markedly from case to case, and from area to area in the same case. The tumor may be composed exclusively of one of the three components, and may be descriptively diagnosed as lipoma, leiomyoma or hemangioma.10 Some cases of AML have been reported as ‘capsuloma’ that are composed exclusively of SMC-like cells. This is also referred to as leiomyomatous AML.6–8,10 According to the previous reports, the tumor is well-circumscribed without a fibrous capsule, and has a white cut surface.7,8,10 Histologically, the tumor is composed predominantly of spindle-shaped SMC-like cells with an interlacing fascicular growth pattern, mimicking true leiomyoma, with epithelioid SMC-like cells with spherical nuclei and eosinophilic, often clear without atypism. Immunohistochemically, tumor cells are reactive with HMB-45 antibody, which provides a crucial marker for differential diagnosis from true leiomyoma.7,8,10
The authors thank Mr Itaki, Ms Yamasaki and Ms Iwatani for their technical and secretarial support.