Oncocytoma

Context.-Adult renal neoplasms have a predilection for older patients and are clinically and morphologically distinct from renal neoplasms found in pediatric age groups. Relatively rare tumors occur in younger adults (18-45 years of age). Whether these renal tumors are morphologically and clinically distinct from those of older adults has been the subject of controversy. Recent modification of the World Health Organization histologic classification and the American Joint Committee on Cancer staging system of adult renal tumors further highlighted the need for case analysis in this age group.

Objective.-To analyze renal tumors in younger adults based on a large surgical series from a single institution.

Design.-Of 780 renal mass nephrectomy (partial, total, or radical) specimens that were available for evaluation and had been obtained between 1986 and 2004 at Loyola University Medical Center, 112 specimens were from patients between 18 and 45 years of age. The tumors were reevaluated according to the 2004 World Health Organization classification and the 2002 American Joint Committee on Cancer staging system.

Results.-The likelihood of clear cell renal cell carcinoma was significantly reduced from 65% in older adults to 53% in younger adults (18-45 years, P = .04). The reduction trend was more significant when comparing an even younger age group. The majority (64%) of clear cell renal cell carcinoma in younger adults was low stage, T1a. Seventeen percent of these tumors had multilocular cystic features involving more than 50% of the tumor volume (55%-85%). The number of oncocytomas was also significantly lower in younger adults than in older adults (2% vs 11%, P

Conclusions.-Renal neoplasms are more heterogeneous in younger adults and have a different distribution pattern compared with that in older adults. Malignant and benign renal neoplasms tend to have a contrasting sex distribution in younger adults.

(Arch Pathol Lab Med. 2005;129:487-491)

Renal tumors are most frequently encountered in patients between the ages of 50 and 70 years and are rare in children and young adults, with the exception of Wilms tumor. The new World Health Organization (WHO) classification1 and the American Joint Committee on Cancer (AJCC) staging system2 for adult renal tumors are expected to promote improvements in predictions of tumor prognosis, therapeutic response, monitoring of recurrence, and patient follow-up. Relatively uncommon tumors arise in younger adults (18-45 years old). Whether these tumors are clinicopathologically different from those in older adults has recently become the subject of intense study.3-6 The recent changes in classification and staging system further warranted reevaluation of renal tumors in younger adults.

Results of several studies have indicated that clear cell renal cell carcinoma (RCC) is the most common tumor in this age group and appears to have a favorable prognosis despite symptomatic presentation in the majority of cases.3-6 However, the difference between younger and older adults in terms of the prevalence of tumor types was not addressed in these studies. The objective of the present study was to analyze the renal tumors encountered at a single institution with regard to their demographic distribution and morphology according to the 2004 WHO classification and the 2002 AJCC staging system. Because of a possible clinicopathologic distinction between neoplasia affecting younger adults and that affecting older adults, we compared the spectrum of pathology found in renal tumors from these 2 age groups.

MATERIALS AND METHODS

Seven hundred eighty nephrectomy (partial, total, and radical) specimens obtained for renal parenchymal masses between 1986 and 2004 at Loyola University Medical Center were available for evaluation. Of these, 112 (14%) specimens were from patients between 18 and 45 years of age. Archival slides were reevaluated according to the 2004 WHO classification and the 2002 AJCC staging system. Immunohistochemical and special stains were used where applicable. Immunohistochemical stains utilized were pankeratin (prediluted; AEl/AE3, Ventana, Tucson, Ariz), cytokeratin 7 (prediluted; K72, Cell Marque, hot Springs, Ark), cytokeratin 34J3E12 (1:50; Cell Marque), vimentin (prediluted; 3B4, Ventana), smooth muscle actin (prediluted; 1A4, Zymed, San Francisco, Calif), anti-melanosomes (prediluted; HMB-45, Ventana), SlOO protein (prediluted; 4C4.9, Cell Marque), synaptophysin (prediluted; Ventana), CDlO (prediluted; 56C6, Ventana), CD56 or neural cell adhesion molecule (1:100; 123C3, Zymed), CD57 (prediluted; NKl, Cell Marque), CD99 (prediluted, 1:50 to 1:75; 12E7, Dako, Carpinteria, Calif), CD117 (1:50; c-Kit, Dako), TFE3 (1:200; anti-hTERT antibody, Santa Cruz Biotechnology, Santa Cruz, Calif), Ulex eiiropneus lectin type 1 (1:500; UEl-I, Dako), Wilms tumor 1 (1:100; 6F-H2, Dako), estrogen receptor (prediluted; 6Fl 1, Ventana), and progesterone receptor (prediluted; 1A6, Zymed). The special stains used were Halle colloidal iron, trichrome stain, and mucicarmine. Tumor karyotyping, fluorescent in situ hybridization analysis, and electron microscopy studies were performed in selected cases as previously described.7

Differences in distribution of renal tumors between older adults and younger adults were tested using chi-square tests, and the differences were considered significant at P

RESULTS

There were 112 renal specimens from patients 18 to 45 years old. The youngest patient in the series was an 18-year-old with clear cell RCC. There were 59 cases (53%) of clear cell RCC, 13 (12%) papillary RCC (adult type), 9 (8%) chromophobe RCC (in 3 patients with sarcomatoid features), 2 (2%) oncocytoma, and 29 (26%) miscellaneous tumors. The miscellaneous category included TFE3-positive (Xpll.2 translocation) carcinoma (n = 3, Figure 1), renal medullary carcinoma (n = 1, Figure 2), collecting duct carcinoma (n = 4), peripheral neuroectodermal tumor (n = 1, Figure 3), mucinous tubular and spindle cell carcinoma (n = 1, Figure 4), metanephric neoplasms (n = 2, Figure 5), angiomyolipoma (n = 6, 4 tumors were

The distribution of renal tumors in different age groups is illustrated in Figure 7. The incidence of clear cell RCC was significantly lower in younger adults than in older adults (>45 years old) (53% vs 65%, P = .04). The reduction trend was also noticed when comparing an even younger age group (48% vs 65%, P = .01). Sixty-four percent of clear cell RCC in young adults was low stage, TIa. Seventeen percent of clear cell RCC tumors had multilocular cystic features that involved more than 50% of the total tumor volume (55%-85%). The number of oncocytomas was also significantly lower in younger adults than in their older counterparts (2% vs 11%, P

COMMENT

The 2002 AJCC staging system and 2004 WHO classification of tumors of the urinary system incorporate recent advances in our understanding of renal cell neoplasia. Although the current classification system is still primarily based on cytologie appearance and the putative cell of origin in combination with growth pattern, recently discovered genetic alterations played a decisive role in the recognition of new entities. In particular, the spectrum of renal neoplasia affecting younger adults has been expanding. The pathologic features of these new rarer entities are described here.

In a recent study, Rodriguez et al" found that the incidence of clear cell RCC in younger adults was significantly lower than that in older adults (69% vs 91% in their study). Results of our study confirm that the rate of clear cell RCC is reduced in younger adults. We also found that the reduction trend was more significant when comparing an even younger age group. The majority of clear cell RCC in younger adults in our patient population was at a lower stage, TIa (64%). Rodriguez et al5 and Yusim et al6 also demonstrated that the younger the patient age the lower the tumor stage at the time of diagnosis.

The 2004 WHO classification of renal tumors includes a description of multilocular cystic RCC as a distinct tumor composed entirely of numerous cysts, the septa of which contain small groups of low-grade clear cell carcinoma.1 Multilocular cystic RCC, as currently defined, is a relatively rare neoplasm (50%; range, 55%-85%). It is not clear whether the presence of such cystic components is associated with a better outcome than that for solid tumors.

Oncocytoma also had a significantly lower incidence in younger adults compared with older adults (2% vs 11%, P

In our series, younger adults had a much higher incidence of miscellaneous tumors (26%) than did older adults (4%, P

In our series, more benign (or favorable prognosis) miscellaneous neoplasms tended to occur in younger female adults than in their male counterparts (64% vs 36%, P

Metanephric adenoma, a benign cellular epithelial tumor composed of small uniform acini with embryonal appearance, also has a 2:1 female preponderance.1 This neoplasm belongs to the group of metanephric tumors encompassing (in addition to metanephric adenoma) metanephric adenofibroma, metanephric adenosarcoma, and metanephric stromal tumors. In our series, one younger female patient had a single metanephric adenosarcoma, a biphasic neoplasm with a benign metanephric epithelial component and a clearly malignant stromal component (Figure 5).7

The results of this study indicate that renal tumors are more heterogeneous in younger adults and have a distribution pattern different from that found in older adults. Malignant and benign renal neoplasms tend to have a contrasting sex distribution in younger adults. XpI 1.2 translocation carcinoma, renal medullary carcinoma, primitive neuroectodermal tumor, cystic nephroma, metanephric biphasic tumor, and mucinous tubular and spindle cell carcinoma were seen exclusively in younger adults. As the classification of the renal neoplasms evolves and new entities are recognized, it is particularly important that the diagnosis of renal tumors in younger adults be based on careful pathologic examination incorporating thorough tumor sampling, immunohistochemistry, and whenever possible cytogenetic and molecular studies.

References

1. EbIe JN, Sauter G, Epstein Jl, Sesterhenn IA, eds. Pathology and Genetics of Tumours of the Urinary System and Male Cenital Organs. Lyon, France: IARC Press; 2004. World Health Organization Classification of Tumours: vol 7.

2. Greene FL, Page DL, Fleming ID, et al, eds. A)CC Cancer Staging Manual. 6th ed. New York, NY: Springer.

3. Schiff M, Herter G, Lytton B. Renal adenocarcinoma in young adults. Urology. 1985:25:357.

4. Eggener SE, Rubenstein |R, Smith ND, et al. Renal tumors in young adults. J UmI. 2004:171:106-110.

5. Rodriguez A, Patard D, Lobel B. Renal cell carcinoma in young adults: incidence, disease outcome and review of the literature. Arch Esp UmI. 2002;55: 969-975.

6. Yusim I, Mermershtain W, Neulander E, Eiderberg I, Gusakova I, Kaneti J. Influence of age on the prognosis of patients with renal cell carcinoma (RCC). Onkologie. 2002)25:548-550.

7. Picken MM, Curry JL, Lindgren V, Clark Jl, EbIe JN. Metanephric adenosarcoma in a young adult: morphologic, immunophenotypic, ultrastructural, and fluorescence in situ hybridization analyses: a case report and review of the literature. Am I Surg Pathol. 2001:25:1451-1457.

8. Amin MB, Crotty TB, Tickoo SK, Farrow GM. Renal oncocytoma: a reappraisal of morphologic features with clinicopathologic findings in 80 cases. Am I Surg Pathol. 1997;21:1-12.

9. Lindgren V, Paner GP, Omeroglu A, et al. Cytogenetic analysis of a series of 13 renal oncocytomas. I UmI. 2004:171:602-604.

10. Argani P, Antonescu CR, Couturier J, et al. PRCC-TFE3 renal carcinomas: morphologic, immunohistochemical, ultrastructural, and molecular analysis of an entity associated with the t(X;1)(p11.2;q21). Am I Surg Pathol. 2002:26:1553-1566.

Ying Cao, MD, PhD; Gladell P. Paner, MD; Kent T. Perry, MD; Robert C. Flanigan, MD; Steven C. Campbell, MD, PhD; Maria M. Picken, MD, PhD

Accepted for publication December 2, 2004.

From the Departments of Pathology (Drs Cao, Paner, and Picken) and Urology (Drs Perry, Flanigan, and Campbell), Loyola University Chicago Medical Center, Maywood, III.

The authors have no relevant financial interest in the products or companies described in this article.

Reprints: Maria M. Picken, MD, PhD, Department of Pathology, Room 2242, Building 110, Loyola University Medical Center, 2160 South First Ave, Maywood, IL 60153 (e-mail: mpicken@lumc.edu).

Copyright College of American Pathologists Apr 2005
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