Sarcomatoid Renal Cell Carcinoma of Papillary Origin: A Case Report and Cytogenetic Evaluation.A Case Report and Cytogenetic cytogenetic /cy·to·ge·net·ic/ (-je-net´ik)
1. pertaining to chromosomes.
2. pertaining to cytogenetics.
pertaining to or originating from the origin and development of the cell. Evaluation
Sarcomatoid renal cell carcinoma renal cell carcinoma
Malignant tumour of the cells that cover and line the kidney. It usually affects persons over age 50 who have vascular disorders of the kidneys. It seldom causes pain, unless it is advanced. (SRCC) is an uncommon but particularly aggressive variant of renal cell carcinoma, accounting for 1% to 5% of all renal malignant neoplasms[1-5]; until recently, SRCC was thought to represent a primary renal sarcoma,[6,7] but since these tumors coexpress both epithelial and stromal Stromal
A type of tissue that is associated with the support of an organ.
Mentioned in: Wilms' Tumor markers, they are now believed to represent a form of dedifferentiated carcinoma. Mostly sarcomatoid carcinomas are found in association with conventional (clear cell) renal carcinoma, but there are occasional descriptions of sarcomatoid transformation of chromophobe chromophobe /chro·mo·phobe/ (-fob) any cell or tissue not readily stainable, such as the chromophobe cells in the adenohypophysis.
chro·mo·phobe or chro·mo·pho·bic
adj. carcinoma,[8,9] collecting duct carcinoma, and papillary carcinoma.
The classification of renal cell carcinoma has been significantly improved with the introduction of cytogenetic markers specific to each tumor subtype.[12,13] There is, however, limited information regarding the genetic alterations in SRCC. Occasionally, association of non-clear cell tumors with sarcomatoid carcinoma has led to the presumption that the former dedifferentiates to form the latter Genetic studies designed to trace the origin of SRCC in association with papillary tumors are limited to 3 case reports,[14,16] with 2 reports[14,15] suggesting a clear cell origin and all 3 failing to confirm a papillary papillary /pap·il·lary/ (pap´i-lar?e) pertaining to or resembling a papilla, or nipple.
adj similar to a small, nipple-shaped elevation or projection. derivation. In these 3 cases, the 2 tumors (papillary and SRCC) were not separately sampled; hence, comparative cytogenetic analysis between the tumor subtypes could not be performed.
The genetic composition of SRCC is highly variable, and most analyses[14,15] have shown complex chromosomal rearrangements, suggesting the alteration of multiple genes in this transformation. The role of p53 gene mutation is unclear but has been observed in more than 80% of SRCC cases, including a single case report of SRCC in association with papillary carcinoma, which was believed to be of clear cell origin.
We present a detailed histologic, molecular biological, and cytogenetic evaluation of a papillary renal cell carcinoma with associated SRCC, where each tumor type was separately assessed and where the SRCC was clearly evolved directly from the papillary tumor
REPORT OF A CASE
A 78-year-old man with chronic obstructive airway disease was admitted to hospital with an acute respiratory tract infection Noun 1. respiratory tract infection - any infection of the respiratory tract
infection - the pathological state resulting from the invasion of the body by pathogenic microorganisms . Computed tomography of the chest revealed an incidental 5-cm tumor mass in the upper pole of the right kidney. Medical history was noncontributory, and the patient underwent radical nephrectomy. The patient remains well and apparently free of disease 12 months after surgery.
A tumor mass within the kidney extended from the medulla medulla: see brain stem. to the cortex and macroscopically penetrated the renal capsule, extending into the surrounding fat (Figure 1). Toward the renal medulla, the tumor was friable friable /fri·a·ble/ (fri´ah-b'l) easily pulverized or crumbled.
1. Readily crumbled; brittle.
2. Relating to a dry, brittle growth of bacteria. and cystic, whereas in the outer cortex, it was more solid and uniform. The central tumor mass measured 25 x 30 x 20 mm, whereas the more solid perimeter tumor measured 20 x 25 x 18 mm. Fresh tissue from both tumor areas was submitted separately for cytogenetic analysis.
[Figure 1 ILLUSTRATION OMITTED]
Histologic Findings and Immunostains
Sections of the central portion of the tumor confirmed a classic papillary renal cell carcinoma (Figure 2) composed of fine vascular cords lined by bland neoplastic cells with grooved nuclei. By contrast, the solid tumor area was composed of anaplastic an·a·plas·tic
1. Relating to the surgical restoration of a lost or absent part.
2. Of, relating to, or characterized by cells that have become less differentiated.
1. spindle cells with a high mitotic rate, including atypical mitoses (Figure 2). The interface area between the 2 was composed of part papillary and part solid tumor that showed both significant pleomorphism pleomorphism /pleo·mor·phism/ (-mor´fizm) the occurrence of various distinct forms by a single organism or within a species.pleomor´phicpleomor´phous
1. and anaplasia anaplasia /ana·pla·sia/ (-pla´zhah) dedifferentiation; loss of differentiation of cells and of their orientation to one another and to their axial framework and blood vessels, a characteristic of tumor tissue. and areas of coagulative necrosis. Immunostains for cytokeratin (AE1/3, Dako Corporation, Glostrup, Denmark) were positive in both tumors, whereas stains for vimentin (Dako) were only positive in the sarcomatoid region. The interface region was variably stained for both markers.
[Figure 2 ILLUSTRATION OMITTED]
Cytogenetic analysis of 6 cell metaphases from the papillary tumor (central) produced a composite karyotype, 49,X+3, +7,+7,+17 (Figure 3), which is consistent with the diagnosis of papillary renal carcinoma.[12,13] No loss of 17p was detected, a feature associated with progression of papillary carcinoma to high-grade carcinomas. Analysis of 12 metaphases from the solid sarcomatous region gave a composite karyotype of between 114 and 116 chromosomes (ie, based on a triploid triploid /trip·loid/ (trip´loid) having triple the haploid number of chromosomes (3n).
Having three times the haploid number of chromosomes in the cell nucleus.
n. karyotype): 114-116, XX, + X, -1, -1, + del(1p)x6, -2, + der(2)t(2;3) , +5, +5, +6 +7, +7, +7, +7, +7, +7, +8, +9, +13, +14, +17, +17, +18, +19, +20, +21, +21, -22[cp12] (Figure 3). There was no loss of 3p, and multiple copies of 7 and 17 are consistent with the tumor's papillary origin.
[Figure 3 ILLUSTRATION OMITTED]
Loss of Heterozygosity Loss of heterozygosity (LOH) in a cell represents the loss of one parent's contribution to part of the cell's genome. LOH can arise via several pathways, including deletion, gene conversion, mitotic recombination and chromosome loss. Analysis
DNA DNA: see nucleic acid.
or deoxyribonucleic acid
One of two types of nucleic acid (the other is RNA); a complex organic compound found in all living cells and many viruses. It is the chemical substance of genes. was isolated from neoplastic neoplastic /neo·plas·tic/ (ne?o-plas´tik)
1. pertaining to a neoplasm.
2. pertaining to neoplasia.
pertaining to neoplasia or a neoplasm. and normal kidney tissue; 20-[micro]m sections were cut from paraffin-embedded tissue samples, each dewaxed in xylene xylene (zī`lēn) or dimethylbenzene (dī'mĕthəlbĕn`zēn), C6H4(CH3)2 , and DNA prepared as previously described. Loss of heterozygosity for chromosome 3p was determined by polymerase chain reaction polymerase chain reaction (pŏl`ĭmərās') (PCR), laboratory process in which a particular DNA segment from a mixture of DNA chains is rapidly replicated, producing a large, readily analyzed sample of a piece of DNA; the process is amplification of polymorphic microsatellite See miniaturized satellite. markers and gel electrophoresis as previously described. Markers used in this study were D3S1297 (3pter-3p22.5), D3S1539 (3pter-3p22.5), D3S1514 (3p21-3p14.2), and D3S1478 (3p21.3-3p21.2). No loss of heterozygosity was observed at D3S1297, D3S1514, or D3S1478. The patient was homozygous ho·mo·zy·gous
Having the same alleles at one or more gene loci on homologous chromosome segments.
Identical genes controlling a specified inherited trait. at D3S1539. These results indicate retention of heterozygosity heterozygosity /het·ero·zy·gos·i·ty/ (het?er-o-zi-gos´i-te) the state of possessing different alleles at a given locus in regard to a given character.heterozy´gous
n. of chromosome 3p with no deletion of this chromosome fragment.
p53 mutations within exons 4 to 8 were screened using a polymerase chain reaction--single-stranded conformational polymorphism detection system. Both sarcomatous and papillary regions were separately assessed and showed no p53 mutations. Further, immunostains with anti-p53 (D-7, Dako) were negative in both tumor subtypes.
Sarcomatoid renal cell carcinoma is considered a late and almost invariably fatal cancer, with a mean survival time of less than 6 months. It usually evolves from conventional (clear cell) renal cell carcinoma. Although it is acknowledged that SRCC may be associated with multiple renal tumor subtypes of differing biological behavior, direct evolution from non-clear cell tumors has not previously been proven, and SRCC remains classified as a single pathological entity with a uniformly poor prognosis. This case represents the first cytogenetic evidence of direct progression of papillary renal carcinoma (non-clear cell) to SRCC as determined by cytogenetic analysis.
Using standard cytogenetics cytogenetics /cy·to·ge·net·ics/ (-je-net´iks) the branch of genetics devoted to cellular constituents concerned in heredity, i.e. chromosomes. , loss of chromosome 3p, a specific genetic change associated with the clear cell subtype, was not detected in 12 metaphases from the sarcomatoid component. As has been previously indicated, discrepancies between metaphases of primary cultures are not uncommon. Therefore, we assessed 12 separate metaphases in conjunction with whole tissue loss of heterozygosity to exclude possible error The loss of heterozygosity method further excludes minor deletions in the 3p region that may not be evident with standard cytogenetic evaluation.
A previous description of SRCC associated with papillary renal cell carcinoma cited multiple defects in chromosomes 1q, 12q, 16p, and 19p that are not seen in our case. This previous analysis was performed on a metastatic tumor site, and cytogenetic evaluation of the primary "mixed glandular-papillary-sarcomatoid" lesion was not performed.
In the current case, multiple and complex genetic changes have occurred in the transformation of papillary carcinoma to SRCC, but multiple copies of chromosome 7 and 17 are retained. Further, no specific genetic changes previously reported as characteristic of SRCC are recognized. Since progression of non-clear cell carcinoma to SRCC is uncommon and not well investigated, genetic and biological differences from SRCC of clear cell origin may well exist. Since our patient is well and without apparent recurrent or metastatic disease 1 year after surgery, the invariably fatal outcome associated with most SRCC (of clear cell origin) may not apply in tumors derived from chromophilic cells. We, therefore, recommend cytogenetic evaluation of all SRCC in addition to routine histologic testing so that the biological behavior can ultimately be defined. Since preoperative diagnosis and distinction from other forms of renal carcinoma are rare, use of loss of heterozygosity techniques and p53 estimation on formalin-fixed tissues may be sufficient to identify SRCC of non-clear cell origin so that follow-up data can be assessed.
We would like to acknowledge Dr Melvyn Kuan for his assistance in the preparation of the manuscript.
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Accepted for publication May 10, 2000.
From the Urological Research Centre, Department of Surgery, University of Western Australia, Nedlands, Western Australia This article is about a suburb of Perth, Western Australia. For the local government area, see City of Nedlands.
Nedlands is a western suburb of Perth, Western Australia. (Drs Cohen cohen
(Hebrew: “priest”) Jewish priest descended from Zadok (a descendant of Aaron), priest at the First Temple of Jerusalem. The biblical priesthood was hereditary and male. , lacopetta, Weinstein, and Dawkins); Department of Urology, Stanford University, Palo Alto, Calif (Dr McNeal); Cytogenetic Services, Hawthorne, Victoria, Australia (Dr Susman); and Department of Pathology, Royal Perth Hospital Royal Perth Hospital (RPH) is an 855-bed teaching hospital located on north eastern edge of the CBD of Perth, Western Australia (). Royal Perth Hospital also has specialised rehabilitation facilities at Shenton Park. , Perth, Western Australia This article is about the metropolitan area of Perth, Western Australia. For the local government area, see City of Perth.
Perth is the capital of the Australian state of Western Australia. (Dr Sellner).
Reprints: Ronald J. Cohen, FRCPA, Urological Research Centre, Level 2, M Block, The Queen Elizabeth II Medical Centre, Nedlands, 6009, Western Australia, Australia (e-mail: email@example.com).