Imprint cytology of the chromophobe renal cell carcinoma: Correlation with the histological and ultrastructural features

Abstract

Chromophobe renal cell carcinoma (ChRCC) is a unique entity of renal cell carcinoma and has a low malignant potential. A correct cytological diagnosis can help to decide the suitable management and operation. I present here a case with an imprint cytology of ChRCC focusing on the correlation with the histological and ultrastructural features. A 69-year-old male underwent partial nephrectomy and imprint cytology. The cellular smear consisted of predominantly granular eosinophilic cells with round nuclei, a well-defined cytoplasmic membrane and accentuated cell borders. The cytoplasm was characterized by variable granularity with reticulated clearing or vague perinuclear vacuolization. Distinct perinuclear halos were infrequently noted. The histological, immunohistochemical and ultrastructural findings were compatible with ChRCC.

Introduction

Chromophobe renal cell carcinoma (ChRCC) is a unique entity of renal cell carcinoma (RCC). The ChRCC is composed of an admixture of two types of tumor cells with a prominent cell membrane in varying proportions.[1,2] One type is large pale cells and the other type is smaller granular eosinophilic cells. It is sometimes difficult to distinguish ChRCC from renal oncocytoma and other RCCs with granular cells, cytologically and, also, histologically.[3–5] I present here a case with an imprint cytology of the ChRCC, focusing on the correlation with the histological and ultrastructural features.

Case Report

A 69-year-old male presented with abdominal discomfort and he was hospitalized under the clinical impression of acute cholangitis. Bilateral exophytic renal masses were incidentally found on the abdominal computed tomography. The renal masses measured 7.7 cm and 5.5 cm in the greatest dimension at the right lower and left upper poles, respectively. Bilateral RCC was suggested radiologically. Cholecystectomy and left partial nephrectomy were performed. The partial nephrectomy specimen revealed a well-circumscribed, homogeneously tan brown solid mass that measured 6×6×5.5 cm [Figure 1]. There was no central scar, hemorrhage or necrosis.

Figure 1.

Macrophotograph showing a well-circumscribed, brown, solid renal mass

The imprint cytologic preparation was made. The smears were highly cellular and the tumor cells were arranged in monolayered sheets or as single cells. The tumor cells were polygonal and they had abundant granular eosinophilic cytoplasm, a well-defined cytoplasmic membrane and accentuated cell borders [Figure 2]. The cytoplasm exhibited variable granularity with reticulated clearing or vague perinuclear vacuolization [Figure 3]. Distinct perinuclear halos were infrequently noted. Typical clear cells were not observed. The nuclei were located eccentrically with variation of their size. The nuclei were round or ovoid with a smooth to mildly irregular nuclear membrane, and markedly wrinkled nuclei were infrequently seen. Mitosis was rarely observed. Nuclear pleomorphism was mostly mild, but it was sometimes marked. Binucleation was frequently noted. Small to large nucleoli were occasionally observed. The background was clean without necrosis or inflammation.

Figure 2.

Microphotograph from the cytology smear showing sheets composed of polygonal tumor cells with abundant granular cytoplasm, round nuclei and well-defined cytoplasmic membrane (Papanicolaou, ×400)

Figure 3.

Microphotograph from the cytology smear showing eosinophilic granular cells with reticulated cytoplasmic clearing, vague perinuclear vacuolization (arrows) and mutinucleation (H and E, ×400)

Histologically, the tumor consisted of predominantly eosinophilic granular cells arranged in a solid or nested pattern. The cytoplasmic membrane was well defined and the cell borders were diffusely accentuated. The tumor cells had round, often binucleated nuclei with a small nucleolus. On higher magnification, the cytoplasm exhibited reticulated cytoplasmic clearing or flocculent perinuclear vacuolizations [Figure 4]. Distinct perinuclear halos were inconspicuous. Immunohistochemically, the tumor cells were diffusely positive for pancytokeratin and cytokeratin 7 and focally positive for CD10 but negative for vimentin and epithelial membrane antigen.

Figure 4.

Microphotograph of histology showing solid growth of eosinophilic granular cells with reticulated cytoplasmic vacuolization and accentuated cell borders (H and E, ×400)

On electron microscopy, the tumor cells had round to oval nuclei with smooth to focally irregular nuclear membrane and occasional small nucleoli. The cytoplasm was packed diffusely with numerous microvesicles admixed with a considerable amount of mitochondria and intermediate filaments [Figure 5]. The mitochondria were scattered randomly without peripheral condensation. Some tumor cells exhibited globular aggregates of microvesicles that seemed to push their nucleus [Figure 6]. The plasma membrane was highlighted by complex plication. The histological, immunohistochemical and ultrastructural findings were compatible with ChRCC.

Figure 5.

Electron microphotograph showing numerous microvesicles, scattered mitochondria and complexly plicated plasma membrane (arrows) (×6000)

Figure 6.

Electron microphotograph showing a globular aggregate of microvesicles (arrows) pushing the nucleus (×3500)

Right-sided partial nephrectomy was performed 3 months later. Macroscopically, the tumor was golden yellow and histologically, it was diagnosed as clear cell RCC.

Discussion

ChRCC has unique morphological, histochemical, ultrastru-ctural and cytogenetic characteristics.[2,3] Ultrastructurally, ChRCC contains numerous microvesicles, which account for the diffuse and strong reaction with Hal's colloidal iron stain.[6] Cytomorphologically, ChRCC is composed of polymorphous voluminous cells with distinct cell borders. The cytoplasm exhibits either a pale, finely reticular and almost transparent appearance or a granular eosinophilic appearance.[1,7,8] Cytomorphologically, the distinct perinuclear halo and wrinkled nuclei are important diagnostic clues.[1,4,7] The perinuclear halos of ChRCC reflect numerous cytoplasmic microvesicles and perinuclear rarefaction and peripheral condensation of mitochondria on electron microscopic examination.[6] In the present case, however, perinuclear halos and wrinkled nuclei were not conspicuous, causing some confusion with renal oncocytoma and other RCCs with granular cells. The indistinct perinuclear halo may reflect the lack of peripheral condensation of mitochondria on the electron microscopic examination. In the present case, numerous microvesicles were packed diffusely or aggregated globularly and a considerable amount of mitochondria were scattered randomly without peripheral condensation. This ultrastructural feature may be responsible for the cytomorphology of the reticular cytoplasmic clearing or the vague perinuclear vacuolization that can also be an important diagnostic clue in distinguishing ChRCC from other renal tumors. Based on the previous reports and the present case, another unique characteristic cytomorphology of ChRCC is a thick, well-defined cell membrane, which reflects a complex plication of the cell membrane on electron microscopic examination.[2,7]

Cytologically, the main differential consideration of the ChRCC includes renal oncocytoma and clear cell RCC with granular cells. The distinction from oncocytoma is most important and challenging. However, renal oncocytoma has a monotonous population of cells with uniform nuclei and the cytoplasm of renal oncocytoma has homogeneous granularity without reticulated clearing or vacuolization characterized by that of the ChRCC.[5,7] Binucleation and an accentuated cell border are not as prominent in renal oncocytoma as that of ChRCC.[5,9] It is difficult to distinguish between ChRCC and clear cell RCC with predominantly granular cells. However, the cytoplasm of clear cell RCC is friable and the cells show indistinct cell borders on the cytologic smear.[5] Clear cell RCC is often associated with a dirty, bubbly background with many foamy histiocytes, and this in contrast to the clean background of ChRCC.[5] Immunohistochemical stains on the cytologic smear or cell block can be used for making the differential diagnosis. The positivity for vimentin can distinguish ChRCC and renal oncocytoma from clear cell RCC.[3]

The prognosis of ChRCC is intermediate between renal oncocytoma and clear cell RCC.[2,9] ChRCC has a low malignant potential and the treatment of ChRCC is usually simple nephrectomy or partial nephrectomy.[1] Renal oncocytoma is a benign tumor.[9] It is sometimes important to distinguish ChRCC from renal oncocytoma on the pre- or intra-operative cytologic smear.[5] A correct cytological diagnosis can help to decide the suitable management or operation. Particularly, if bilateral renal masses are present, like was present in our patient, or the contralateral kidney is non-functional or absent, then a minimal operation is essential to preserve the renal function.