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0 1992 The Japanese Society of Pathology

Papillary Renal Cell Carcinoma Report of Two Cases

Toshiharu Matsumoto', Tetsuo Iijimal, Noriyuki Kuwabara', Yoshiaki Wakumoto2, Takeshi Fukushima2, Yoshirou Sakamoto2, Ryuichi Kitagawa2, Keiko Ta keda3, Yachiyo Oonuma3, and Setsuko Suzuki3

Papillary renal cell carcinoma is an uncommon variant of renal cell carcinoma which has unique features including hypovascularity or avascularity, extensive stromal macro- phage infiltration and better prognosis than that for nonpapillary renal cell carcinoma. Two cases of papillary renal cell carcinoma presenting hypovascular or avascular angiology are presented. Histologically, the two tumors had a purely papillary structure. Papillae were lined by a layer of epithelial cells which lacked prominent cellular atypia, and there were numerous macrophages in the stroma. In addition, in one patient, extensive calcification of the tumor capsule was present. Furthermore, our expe- rience in the present study with imprint cytology indicates that it offers corroborative information for the intraoper- ative diagnosis made on the basis of frozen section exami- nation. Acta Pathol Jpn 42 : 298-303, 1992.

Key words : Papillary renal cell carcinoma, Pathology, Imprint cytology

Renal cell carcinoma is the most common primary malignancy of the kidney. Papillary renal cell car- cinoma is an uncommon variant of renal cell carcinoma, which may simulate benign lesion on angiography because of poor or absent blood supply. There are morphological and biological differences between papil- lary and nonpapillary renal cell carcinoma, and follow-up data demonstrate higher survival rate for patients with papillary than that for those with nonpapillary renal cell

Received August 21, 1991. Accepted for publication December 3, 1991. 'First Department of Pathology and *Department of Urology, Juntendo University, School of Medicine, Tokyo. Wnical Laboratory, Juntendo University Hospital, Tokyo. Mailing address: Toshiharu Matsumoto, M.D., First Depart- ment of Pathology, Juntendo University, School of Medicine, Hongo 2-1-1, Bunkyo-ku, Tokyo 113, Japan.

carcinoma. Approximately 166 cases of papillary renal cell carcinoma have been reported in the international literature(1-14). In Japan, 10 cases have been report- ed in the literature (1 5-20), but none of them have been recorded in pathological articles. Thus, we present clinico-pathologic findings in two cases of papillary renal cell carcinoma.

CLINICAL SUMMARY

Case 1

A 44-year-old man was noted to have a cystic-appear- ing renal mass by ultrasound examination performed during a health check-up in 1988. He had no symp toms of renal disease. In December, 1990, both ultra- sound and computed tomography (CT) indicated that the mass was a solid lesion. On January 7, 1991, the patient was admitted to the Department of Urology at Juntendo University Hospital. Intravenous pyelogram showed a mass in the mid-portion to lower pole of the right kidney which displaced and compressed the calyces of those areas, and both ultrasound and CT demonstrat- ed a solid mass in the same area. Selective right renal arterogram revealed a 4.5 cm hypovascular mass with stretching of the mid-portion and lower pole vessels. On January 24, 1991, right radical nephrectomy was performed. The patient had an uneventful postoperative course and is alive, without evidence of tumor recurrence, about 6 months after surgery.

Case 2

A 60-year-old male was found to have calcified foci in the left abdominal cavity on a roentgenogram examina- tion of the upper gastrointestinal tract in 1990. He had

Acta Pathologica Japonica 42 (4) : 1992

PATHOLOGICAL no symptoms of renal disease. He was noted to have a solid renal mass on CT performed on April 16, 1991. On May 21, 1991, the patient was admitted to the Department of Urology at Juntendo University Hospital. Case

Intravenous pyelogram showed a mass with a calcified rim in the upper pole of the left kidney. Both ultrasound and CT demonstrated a solid mass with calcification in the same areas. Selective left renal arteriogram revealed a 5 cm avascular mass in the upper pole of the left kidney. On May 30, 1991, left radical nephrectomy was performed. The patient had an uneventful post- operative course and is alive, without evidence of tumor recurrence, about 2 months after surgery.

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FINDINGS

The resected right kidney measured 1 O x 7 x 4 . 5 cm. A well-encapsulated yellowish tumor, 4.5x4.7 x4 cm, was present in the mid-portion to lower pole of the kidney (Fig. 1). The tumor compressed the calyces of the mid-portion and lower pole. Histologically, the tumor had a purely papillary structure. Papillae with delicate connective cores were lined by a single row of cells which had scanty or more abundant and eosinophilic cytoplasm, and round uniform nuclei with a mild degree

Figure 1. Case 1. A wellkencapsulated tumor is present in the mid-portion to lower pole of the right kidney.

Figure 2. Case 1. a : Photomicrograph of the tumor. Note papillary structures with delicate connective cores lined by epithelial cells. (HE) b: High-power view of a. The epithelial cells present scanty or more abundant and eosinophilic cytoplasm and slight nuclear atypia. Note macrophages in the papillae. (HE)

300 Papillary Renal Cell Carcinoma (Matsumoto et a/.)

Figure 3. Case 2. a : Photomicrograph of imprint cytology from renal tumor. Note a papillary cluster of epithelial cells and macrophages (arrows) in the background. (Papanicolaou) b : High- power view of a. The epithelial cells have finely granular or vacuolated cytoplasm and uniform nuclei containing inconspicuous nucleoli. (Papanicolaou)

Figure 5. Case 2. Photomicrograph of the tumor presenting papillary renal cell carcinoma. (HE)

Figure 4. Case 2. A well-encapsulated tumor with necrosis is present in the upper pole of left kidney.

Acta Pathologica Japonica 42 (4) : 1992 301

of nuclear pleomorphism and hyperchromatism (Figs. 2a, b). Three or fewer mitoses per 10 high power fields were observed. Macrophages had infiltrated into approximately one-fourth of all papillae (Fig. 2b). These findings indicated that the tumor was papillary renal cell carcinoma. There were focal areas of necrosis. There was capsular invasion, but no extracapsular or renal vein invasion was noted.

Case 2

For intraoperative diagnosis of the tumor at surgery, both imprints and frozen sections were obtained from a small part of the tumor. Imprint cytology showed that there were papillary clusters of epithelial cells with finely granular or vacuolated cytoplasm and uniform nuclei containing inconspicuous nucleoli (Figs. 3a, b). In addi- tion, numerous macrophages were noted in the back- ground (Fig. 3a). Frozen 'sections demonstrated that papillae were covered by a layer of epithelial cells with scanty or more abundant eosinophilic cytoplasm which represented mild cellular a typia. Numerous macro- phages were also present in the papillae. These findings indicated that the tumor was renal cell carcinoma, which was suspected to be of the papillary type. On the basis of the intraoperative diagnosis of renal cell carcinoma, left radical nephrectomy was performed. The resected left kidney measured 1 2 . 5 x 6 x 5 . 5 cm. A well-encap sulated necrotic yellowish tumor, 6 . 5 x 4 x 4 cm, was present in the upper pole of the kidney (Fig. 4). His- tologically, the tumor had a purely papillary structure. The epithelial cells lining the papillae had eosinophilic or vacuolated cytoplasm, and round nuclei with a mild-to- moderate degree of nuclear pleomorphism and hyper- chromatism (Fig. 5). The number of mitoses in the tumor ranged from five to eight per 10 high power fields. Macrophages had infiltrated into almost all papillae (Fig. 5). These findings corresponded to those of papillary renal cell carcinoma. In addition, there were extensive areas of necrosis and hemorrhage. Extensive calcification was noted in the capsule. Moreover, numer- ous psammomatous bodies were present within the tumor. There was capsular invasion, but there was no extracapsular or renal vein invasion.

DISCUSSION

Renal cell carcinoma accounts for over 90% of all primary malignant neoplasms,of the kidney. This tumor is pathologically classified by the dominant cell type (clear, granular, spindle, or pleomorphic cell), by the cellular arrangement (a Iveolar, tubular, papillary, cystic, or solid), and by the degree of nuclear atypia(21).

Pathologically, a tumor is classified as papillary if vas- cularized connective stalks invested with neoplastic cells comprise at least 50% of the tumor (3). Papillary renal cell carcinoma accounts for 5-1 5% of all neoplasms arising from the tubular epithelium (1, 3, 7). Papillary renal cell carcinoma is generally a slow-growing and well-encapsulated mass which is almost always angio- graphically hypovascular or avascular (2, 3, 5, 6).

Of published studies of papillary renal cell carcinoma, that by Mancilla-Jimenez and co-workers (3) reported the largest number of patients. They studied 34 patients with papillary renal cell carcinoma, of whom 2 3 were male and 11 female. The age range of the patients was 2 7 to 78 years, with a mean age of 52 years. The tumor size ranged from 8 to 2 3 cm, with a mean size of 8 cm. The most outstanding macroscopic feature was the presence of massive necrosis, which was seen in more than two-thirds of the cases. Moreover, in approx- imately one-third of cases, extensive calcification of the capsule was present. Another striking histological finding was the extensive macrophage infiltration of the papillae. Papillary renal cell carcinoma was often at a less advanced stage at detection, and patients had a better prognosis than those with other types of renal cell carcinoma. Concerning survival for renal cell carcinoma in Stagel , they reported that the survival rate for patients with papillary renal cell carcinoma was significantly higher than that for those with nonpapillary tumor, although Silva and Childers (22) reported that the prognosis in patients with papillary and nonpapillary renal cell carcinoma was the same.

At our institution, 84 nephrectomies were performed for renal cell carcinoma between January, 1986 and June, 1991. Among these renal cell carcinomas, two (2.4%) were classified as papillary. Comparison of results at our institution with those reported in a study conducted a t hospitals in the United States (3) reveals that the incidence of papillary renal cell carcinoma at our institution is apparently lower. This difference was significant a t the p=O.Ol level when calculated with the chi-square test.

Stromal macrophage infiltration is apparently a unique feature of papillary renal cell carcinoma, and the infiltrating macrophages are suggested to be engaged in a host defense mechanism against the tumor (3). Moreover, recent studies have shown that papillary renal cell carcinoma is marked by karyotype and DNA changes different f rom those found in nonpapillary renal cell carcinoma. The most pertinent differences are the lack of 3p rearrangement, the absence of trisomy 5q, and the gain of chromosome 1 7 in papillary tumors (23). The role of these chromosome aberrations in the develop ment, progression and phenotypical differentiation of the

302 Papillary Renal Cell Carcinoma (Matsumoto et a/.)

two types of kidney tumors is not yet clear. Of published studies of papillary renal cell carcinoma,

only the study by Flint and Cookinghan (1 1) addressed the cytology o f papillary renal cell carcinoma. The cytologic appearance of papillary renal cell carcinoma is marked by distinctive papillary structures consisting of epithelial cells which appear benign and numerous macro- phages in the background (1 1). On the basis of detailed aspiration cytologic examinations, Flint and Coo king han concluded that papillary renal cell carcinoma can be consistently recognized in cytologic specimens (1 1). Recently, imprint cytology has been increasingly utilized for intraoperative diagnosis (24). Indeed, in Case 2, imprint cytology offered corroborative information of the intraoperative diagnosis made on the basis of frozen sect ion examination.

The histological morphology of papillary renal cell adenoma is extremely similar t o that of papillary renal cell carcinoma (22,23,25). The adenomas are usually less than 3 c m in diameter, and capsular invasion is not present (22, 25). Thus, histological appearances of tumor cells plus determination of tumor size and capsu- lar invasion are necessary to differentiate between the two.

Procedures of operation and chemotherapy do not differ in papillary and nonpapillary renal cell carcinoma. Nonpapillary renal cell carcinoma is usually diagnosed as carcinoma after detailed preoperative examination. On the other hand, in papillary renal cell carcinoma, preoper- at ive diagnosis is frequently difficult because o f hypovas- cularity o r avascularity. Thus, papillary renal cell car- cinoma is frequently diagnosed intraoperatively. It was concluded that in the diagnosis of papillary renal cell carcinoma, clinicians and pathologists must recognize the specific features of papillary renal cell carcinoma, including hypovascularity or avascularity and extensive stromal macrophage infiltration.

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