Fine-needle aspiration of renal masses in adults: analysis of results and diagnostic problems in 108 cases.

Fine-needle aspiration (FNA) biopsy of the kidney has a traditionally well-defined role in the diagnosis and treatment of renal lesions. Recent improvements in renal imaging techniques have also brought renal FNA to the forefront, since small and asymptomatic renal masses are increasingly being detected. Before the physician institutes a treatment plan, such lesions usually require a definitive diagnosis that is best provided by FNA. To assess various aspects of renal FNA, including specimen adequacy, questionable cytologic patterns, and diagnostic pitfalls, we retrospectively evaluate our experience with 108 FNA biopsies performed for the evaluation of renal masses in adults. For each case, the smears were reviewed and correlated with tissue sections from cell blocks, surgical specimens, or autopsy material, when available. The cytologic diagnoses were confirmed by cell block (59 cases), nephrectomy or autopsy (35 cases), or clinical follow-up. Of the 108 FNA biopsy samples, 17 showed evidence of blood, soft tissue, necrotic material, glomeruli, or tubular cells and were classified as unsatisfactory. The following diagnostic categories were noted in the 91 satisfactory aspirates: renal abscess (four cases), benign cyst (30 cases), suspicious lesions (11 cases), and malignant lesions (46 cases). In four cases of renal abscess, FNA found abundant clusters of neutrophils. For the 30 cases interpreted on cytologic evidence as benign cysts, the diagnosis was confirmed in 28 cases; the two remaining cases were acquired cystic kidney and cystic renal-cell carcinoma, respectively. Among the 11 suspicious lesions, the final diagnoses were one benign simple cyst, one angiomyolipoma, two multilocular cystic nephromas, two adult polycystic kidneys, one acquired cystic kidney, three cystic papillary renal-cell carcinomas, and one solid renal-cell carcinoma. Cases classified as suspicious shared characteristic cytologic patterns that distinguished them from simple benign cysts and from classic renal-cell carcinoma. Among the 46 malignant lesions, as evidenced on cytologic examination, 27 were renal-cell carcinomas, five were transitional-cell carcinomas, four were lymphomas, one was a small-cell undifferentiated carcinoma, and nine were metastatic carcinomas. False-positive or false-negative cases were not encountered in this category. In conclusion, FNA is an excellent method to diagnose space-occupying lesions of the kidney. For cystic lesions, cytologic-radiographic correlation is needed to avoid misinterpretation. Our study defines a spectrum of suspicious patterns characteristic of a group of renal lesions that are distinct from both benign simple cyst and straightforward renal malignancy.     

Renal pathology in von Hippel-Lindau disease

Von Hippel-Lindau disease, a rare autosomal disorder, is associated with multiple lesions, including a high incidence of renal lesions and CNS hemangioblastomas. Renal lesions have traditionally been classified as either benign cysts or solid renal cell carcinomas with or without cystic degeneration. We examined seven kidney specimens from four patients with von Hippel-Lindau disease. We found that renal cysts form a histopathologic continuum ranging from benign cysts (with one to two cell layers of bland epithelium), atypical cysts (demonstrating epithelial hyperplasia with or without mild cytologic atypia), to malignant cysts harboring renal cell carcinoma. The presence of atypia or foci of carcinoma does not correlate with cyst size. Lesions that appear radiologically or grossly solid range from conventional solid renal cell carcinoma, sometimes evidencing cystic degeneration, to lesions that are predominantly hyalinized, fibrotic nodules. In contrast to simple cysts occurring in the general population, which are virtually always benign, renal cysts in patients with von Hippel-Lindau disease may contain occult carcinoma. Radiologic evaluation, visual inspection at surgery, and even frozen section analysis of cyst lesions cannot be relied on to detect small foci of carcinoma. The spectrum of pathologic changes and the multicentricity of the renal lesions in von Hippel-Lindau disease complicate the radiologic evaluation and surgical management of these patients.     

Allelic deletions of the VHL gene detected in multiple microscopic clear cell renal lesions in von Hippel-Lindau disease patients.

Patients with von Hippel-Lindau (VHL) disease develop a spectrum of bilateral clear-cell renal lesions including cysts and renal cell carcinomas (RCCs). VHL gene deletions have been previously reported in VHL-associated macroscopic RCC. Although histological analysis suggests that microscopic cystic lesions in the VHL patients may represent precursors of the RCC, there is at present no direct molecular evidence of their relationship. To investigate the relationship between cystic lesions and RCC, 26 microdissected archival renal lesions from two VHL disease patients were studied for loss of heterozygosity at the VHL gene locus using polymerase chain reaction single-strand conformation polymorphism analysis. The renal lesions included 2 benign cysts, 5 atypical cysts, 5 microscopic RCCs in situ, 5 cysts lined by a single layer of cells, in which RCCs in situ were developing, and 2 microscopic and 7 macroscopic RCCs. Except for a single benign cyst, 25 of 26 renal lesions showed nonrandom allelic loss of the VHL gene. In either of the 2 patients, the same VHL allele was deleted in all of the lesions tested, indicating loss of the wild-type allele and retention of the inherited, mutated VHL allele. The results suggest that all clear-cell lesions in the VHL kidney represent neoplasms and that the loss of the VHL gene occurs early in their development. Atypical and benign cysts most likely represent the initial phenotype in malignant transformation to the RCC.     

Ultrasound-guided fine-needle aspiration biopsy remains a valid approach in the evaluation of nonpalpable breast lesions

The use of ultrasound-guided fine-needle aspiration (FNA) biopsy for nonpalpable breast lesions varies considerably. This retrospective study stresses the role of breast FNA in evaluating sonographically suspicious nonpalpable breast masses using a probabilistic reporting system. One hundred and eight consecutive ultrasound-guided FNA biopsies diagnosed as positive (32), suspicious (8), atypical (11), benign (55), and unsatisfactory (2) were analyzed and correlated with 61 subsequent surgical specimens. All positive cytologies showed carcinoma on histology; suspicious cases were followed by 5 carcinomas, 2 fibroadenomas, and 1 papillary lesion. Follow-up of atypical cases included 4 carcinomas, 3 fibroadenomas, and 2 papillary lesions, while all 10 biopsies following benign cytology showed fibrocystic changes. Two cases with suspicious sonographic findings but unsatisfactory cytology had lobular carcinoma. The remainder of the benign and atypical cases were followed clinically and radiographically for at least 10 months and had no evidence of carcinoma. Positive predictive values were positive, 100%; suspicious, 63%; atypical, 36%; benign, 0%. Most (40/43; 93%) carcinomas were invasive. In conclusion, ultrasound-guided FNA for nonpalpable breast lesions is highly accurate, and probabilistic reporting helps direct patient management.     

ThinPrep evaluation of fluid samples aspirated from cystic ovarian masses

The cytological evaluation of ovarian cystic fluid using ThinPrep has not been reported. To determine the diagnostic accuracy of ThinPrep cytology in distinguishing between benign and nonbenign ovarian cystic lesions, we examined 65 fluid samples aspirated during intraoperative consultation with subsequent histologic correlation. One ThinPrep slide was prepared from each sample aspirated from surgically removed ovarian cystic masses and reviewed blindly by a panel of three cytopathologists. The parameters used in cytological evaluation were cellularity, cell types, cellular arrangement, and background. Four samples were acellular and excluded from the study. The consensus cytologic diagnoses were compiled for 61 cases which were assigned to one of the following diagnostic categories: negative for malignant cells (40 cases), atypical cytology (13 cases), and suspicious or positive for malignancy (8 cases). Histologic correlation of the cytological benign/negative cases showed that 26/40 (65%) were histologically benign and 14/40 were false-negative (35%, 5 carcinomas and 9 borderline tumors) with 10 of these cases being mucinous tumors. Most false-negative cytologic samples (11/14 or 79%) did not have an epithelial component. Of the 21 cytological nonbenign diagnoses (atypical/suspicious/positive), 15 (71%) were confirmed on histology (10 carcinomas and 5 borderline tumors). However, a nonbenign cytologic diagnosis was rendered in 6 histologically benign cases, including 2 serous cystadenomas, 1 mucinous cystadenoma, 1 serous cystadenofibroma, 1 endometriosis, and 1 corpus luteal cyst. The diagnostic sensitivity by ThinPrep evaluation of ovarian cystic masses is 81% (26/32) for benign and 52% (15/29) for nonbenign lesions. Our results concluded that ThinPrep examination of ovarian cystic fluid is not accurate in distinguishing benign from malignant cysts, given the significant number of false-negative diagnoses. Major contributing factors include sparse cellularity of the fluid samples and mucinous differentiation of the tumors.     

Accuracy of cytologic diagnoses made from touch imprints of image-guided needle biopsy specimens of nonpalpable breast abnormalities

We investigated the diagnostic utility and accuracy of touch imprints (TIs) prepared from core-needle biopsy (CNB) specimens of nonpalpable breast abnormalities. We reviewed air-dried, Diff-Quik-stained TIs prepared from 172 consecutive CNB specimens obtained with stereotactic or sonographic guidance. Using criteria established for fine-needle aspirates, TIs were categorized as benign, atypical, suspicious, malignant, or unsatisfactory (i.e., showing fewer than six benign epithelial cell clusters or cell distortion). Cytologic diagnoses of TIs were then correlated with the histologic diagnoses of corresponding CNB specimens. CNB specimens were histologically diagnosed as carcinoma (102 cases), benign (59 cases), low-grade phyllode tumor (six cases), and atypical ductal hyperplasia (five cases). TIs were cytologically diagnosed as malignant (63 cases), benign (35 cases), suspicious (19 cases), atypical (18 cases), and unsatisfactory (37 cases). Correlation of the cytologic and histologic diagnoses showed that five TIs diagnosed as benign were false-negative results for histologically diagnosed carcinomas (four cases) and phyllodes tumor (one case). False-negative results were attributed to poor representation of malignant cells. Two TIs diagnosed as suspicious were false results for two histologically diagnosed fibroadenomas. The false suspicious findings resulted from TIs with high cellularity, cytologic atypia, or no familiar (i.e., as seen on fine-needle aspirates) smear pattern. Unsatisfactory TIs were noted in both benign (44%) and malignant (11%) CNB specimens. When lesions categorized as suspicious were grouped with the malignant cases and those classified as atypical were grouped with the negative cases, TI sensitivity and specificity, were 83% and 95%, respectively. Fibroadenomas are difficult to identify on TIs and are likely to be misdiagnosed as suspicious. While high- and intermediate-grade carcinomas are easily categorized using TIs, low-grade carcinomas are best categorized as suspicious because of overlapping cytologic features with proliferative breast lesions. Increased experience with cytologic analysis of TIs improves the accuracy of cytologic diagnoses.     

Abundant intracytoplasmic hemosiderin in both histiocytes and neoplastic cells: A diagnostic pitfall in fine-needle aspiration of cystic papillary renal-cell carcinoma

Benign renal tubular cells and renal-cell carcinomas (RCC) may have intracytoplasmic hemosiderin (ICH). The RCC subtype most commonly reported to contain ICH is papillary carcinoma (PRCC). PRCC, usually a low-grade neoplasm, may be associated with cystic degeneration, hemorrhage, and presence of abundant hemosiderin-laden macrophages (HLM). We report a case of PRCC with massive ICH and HLM that created a diagnostic challenge to differentiate from a hemorrhagic cyst. Review of 14 additional nephrectomy specimens with PRCC disclosed ICH in 3 cases. All had coexisting cystic change and hemorrhage. Preoperative FNA had been performed in one of these cases, and both ICH and HLM were found. Papillary epithelial cell features, however, were well-defined in this case. PRCC should be considered in the differential diagnosis of cystic renal lesions with hemosiderin-laden cells. Differentiation of HLM from neoplastic cells with massive ICH may be difficult, especially when epithelial fragments are scanty.     

Aspiration cytology of cystic carcinoma of the breast

Cystic carcinomas of the breast are rarely encountered in fine-needle aspiration (FNA) biopsies. The most common entities comprise intracystic papillary adenocarcinoma, ductal adenocarcinoma with cystic degeneration including comedo forms of ductal adenocarcinoma in situ, medullary carcinoma, squamous carcinoma, and cystic hypersecretory ductal adenocarcinoma. The cytologic diagnosis is often hampered by sparse cellularity, abundant obscuring blood, necrotic debris, and degenerative changes in diagnostic cells. We report on the cytologic features of 10 cases of cystic carcinoma, including 12 FNA biopsies with radiologic and surgical correlation. The original cytologic diagnoses for these cases were: benign (2 cases), atypical (2 cases), suspicious (3 cases), and positive for malignant cells (3 cases). On repeat FNA, one benign case and one atypical case were reclassified, respectively, as atypical and suspicious for carcinoma. The follow-up diagnoses were 5 intracystic papillary adenocarcinomas and 5 cystic ductal adenocarcinomas. Despite 2 false-negative cases, all cases were adequately managed. Correlation with clinical and radiologic findings and direct sampling of any solid component of these cystic neoplasms are crucial in diagnosis and management.     

Needle aspiration cytology of the irradiated breast.

During a 3-year period (1987-1989), 60 fine-needle aspiration biopsies (FNAs) were obtained from new breast lesions in patients previously treated by radiation and surgery for breast carcinoma. The lesions occurred at or near the site of previous excision, 3-117 months after initiation of radiotherapy. FNAs were classified as follows: acellular (11); negative (29); atypical (13); suspicious (4); and positive (3). For statistical analysis, acellular, negative, and atypical diagnoses were considered negative findings, and suspicious and positive diagnoses were considered positive findings. On the basis of subsequent biopsy and/or patient follow-up, FNA yielded a sensitivity of 86%, a specificity of 98%, a positive predictive value of 86%, a negative predictive value of 98%, and an efficiency of 97%. Excluding cystic lesions, the most reliable criterion for distinguishing malignant from benign lesions was the abundance of epithelial cells, both singly and in large clusters. Cellular characteristics were less helpful, since nuclear atypia was seen in both benign and malignant lesions. It is concluded that (1) FNA is a reliable technique in the evaluation of the irradiated breast; (2) when performed by an experienced operator, an acellular aspirate may be interpreted as evidence against recurrent carcinoma; and (3) epithelial atypia must be interpreted with caution to avoid a false-positive diagnosis.     

Benign tumors and tumor-like lesions of the adult kidney. Part II: Benign mesenchymal and mixed neoplasms, and tumor-like lesions

In this review article the benign tumors and tumor-like lesions of the adult kidney are discussed. The incidence of benign renal tumors is low, especially when compared to renal cell carcinomas, as most are detected incidentally or at autopsy. Some of these tumors, as their names imply, are unique to the kidney, e.g., renal adenoma, metanephric adenoma, renal oncocytoma, nephrogenic adenofibroma, mesoblastic nephroma, capsuloma, juxtaglomerular cell tumor, renomedullary interstitial cell tumor (medullary fibroma), cystic nephroma, cystic partially differentiated nephroblastoma, and cystic hamartoma of the renal pelvis, while others, such as angiomyolipoma, leiomyoma, hemangioma, lipoma, etc., are not unique to the kidney and show similar morphologic features in the other sites they affect. Of the tumor-like lesions, xanthogranulomatous pyelonephritis, malakoplakia, and renal cysts are the most common. The other entities, such as fibroepithelial polyp, are rare, most having been the topic of case reports. In Part I of this paper the benign epithelial tumors of the kidney were previously discussed. This paper (Part II) is devoted to the benign mesenchymal tumors, mixed mesenchymal and epithelial tumors, and the tumor-like lesions.     

The place of fine-needle aspiration in the preoperative diagnosis of the congenital sublingual teratoid cyst

The term "teratoid cyst" was first used by Meyer in his classification of dysontogenetic cysts of the cervicofacial region, which was based on the type of germinative layers included in the cyst wall. Sublingual location of a dermoid cyst is not common, with an incidence of 1.6%. The teratoid cyst is the least common, accounting for 1.8% of sublingual dermoid cysts, and such lesions are extremely rare in infancy. In our case, a 7-mo-old male infant was referred with a sublingual mass. Ultrasonography yielded a cystic mass with internal echoes but no specific diagnosis. The smears obtained from fine-needle aspiration (FNA) displayed sheets of large, benign-appearing, anucleated and nucleated squamous cells. There were a number of neutrophils, which had no significant importance. No atypical cells were observed. According to the clinical picture and FNA findings, it appeared to be a cystic structure of keratogenous origin and could have been any type of dermoid cyst. The cyst was excised completely by the oral approach. On histopathological examination, the presence of skin appendages along with mature cartilage and respiratory epithelium confirmed the final diagnosis of a teratoid cyst. In conclusion, although FNA is not comparable with computed tomography (CT) and magnetic resonance imaging (MRI), it might be valuable for the diagnosis of lesions occurring in this anatomical location. It is safe, cost-effective, and reliable. FNA is not only able to help selecting the most appropriate surgical method, but also be used as a therapeutic modality in some emergencies or during surgery.     

Fine-needle aspiration cytology of a mediastinal seminoma associated with multilocular thymic cyst

Multiloculated thymic cysts are uncommon lesions that can be either acquired or associated with malignancies. This report describes the fine-needle aspiration (FNA) cytology of a mediastinal seminoma with prominent cystic change, confirmed by surgical pathology examination and ancillary studies performed on both the cytology and tissue specimens. The FNA cytology revealed clusters of malignant oval-to-polygonal-shaped cells with large oval nuclei possessing prominent nucleoli set in a pale-to-eosinophilic cytoplasm. These cells were surrounded by a dense lymphoid infiltrate along with a few noncaseating granulomas. The large malignant seminoma cells stained positive for placental alkaline phosphatase (PLAP) and negative for both low molecular and broad-spectrum cytokeratin. The differential diagnosis of malignancies associated with thymic cysts is presented. To the best of our knowledge, this is the first report of aspiration cytology of a mediastinal seminoma associated with a multilocular cyst.     

Fine-needle aspiration cytology of salivary gland: a review of 341 cases

Three hundred and forty-one salivary gland fine-needle aspiration (FNA) cytology specimens taken over a 6-yr period were reviewed and correlated with clinical and/or histological findings. The aspirates were derived from parotid gland (212 cases), submandibular gland (124 cases), and minor salivary gland (5 cases). The major diagnostic categories were unsatisfactory (10 cases), normal (100 cases), sialadenitis (74 cases), cyst (34 cases), lipoma (5 cases), pleomorphic adenoma (55 cases), Warthin's tumor (36 cases), and malignancy (27 cases). The latter included 14 primary salivary neoplasms (4 lymphomas of mucosa-associated lymphoid tissue (MALT) type, 3 adenocarcinomas, 2 squamous carcinomas, 2 adenoid cystic cacinomas, and one case each of carcinoma ex pleomorphic adenoma, undifferentiated carcinoma, and high-grade mucoepidermoid carcinoma), and 13 metastases, 9 of which were derived from squamous carcinomas of head and neck origin. Clinicopathological review showed that 88 of 91 (97%) benign epithelial tumors and 27 of 31 (87%) malignant neoplasms with adequate FNA sampling were accurately diagnosed cytologically. False-negative results were caused by sampling error (7 cases), most notably in cystic tumors, or were due to misinterpretation of uncommon neoplasms (3 cases). The overall sensitivity, specificity, and accuracy were 92%, 100%, and 98%, respectively. FNA cytology provides accurate diagnosis of most salivary gland lesions and contributes to conservative management in many patients with nonneoplastic conditions.     

ThinPrep for cytologic evaluation of follicular thyroid lesions: correlation with histologic findings

Fine needle aspiration (FNA) is often the first step in management of a thyroid nodule. Although papillary carcinomas have distinctive features on conventional smears as well as ThinPrep preparations, cytopathologists rely on the architectural arrangement of cells to classify follicular lesions. The accuracy of ThinPrep in this regard has not been determined. We reviewed all thyroidectomy specimens from a 22-mo period that showed a follicular lesion and had one or more preoperative FNA. The architecture of the lesions on histology was classified as predominantly (>70%) macrofollicular (MA), predominantly microfollicular (MI), mixed (MX), or cystic (C). The presence of colloid, Hürthle cell features, cystic change, Hashimoto's thyroiditis, and nonspecific lymphocytic thyroiditis were also recorded. All FNA specimens were processed with the ThinPrep(R) method and were categorized as nondiagnostic, benign (MA or MX), indeterminate (due to suboptimal cellularity), or suspicious (consistent with a microfollicular or Hürthle cell neoplasm) based on cellularity, architectural arrangement of the follicular cells, and the presence or absence of colloid on FNA. Those cytologic specimens in the indeterminate category were subcategorized as suggestive of an MA, MX, or MI lesion if possible. Histocytologic findings were correlated using Fisher's exact test. A total of 95 patients with 115 FNAs were included in the study (mean age: 48 yr; 75 females and 20 males). Seven of the FNAs were nondiagnostic, 23 benign, 69 indeterminate (5, 8, and 30 favor MA, MX, and MI, respectively, 6 cyst contents and 20 not subclassifiable) and 16 suspicious. The cytohistologic correlation for architecture was significant (P = 0.003). The cytohistologic correlation of cystic change, Hürthle cell change, and the presence of colloid (large fragments of colloid and "tissue-paper-like material" on cytology vs. abundant colloid on histology) was highly significant (P < 0.001, < 0.001, and < 0.03, respectively). In conclusion, thyroid FNA with ThinPrep is useful in predicting the architectural pattern of follicular lesions. It is also reliable in predicting cystic change, Hürthle cell change, and the presence of colloid. Watery colloid is probably present as "tissue-paper-like material" in thyroid FNA ThinPrep preparations.     

Renal cystic diseases: a review

This review aims to assist in the categorization of inherited, developmental, and acquired cystic disease of the kidney as well as to provide a pertinent, up-to-date bibliography. The conditions included are autosomal-dominant polycystic kidney disease, autosomal-recessive polycystic kidney disease, unilateral renal cystic disease (localized cystic disease), renal simple cysts, multicystic dysplastic kidney, pluricystic kidney of the multiple malformation syndromes, juvenile nephronophthisis and medullary cystic disease, medullary sponge kidney, primary glomerulocystic kidney disease, and glomerulocystic kidney associated with several systemic disorders mainly of genetic or chromosomal etiology, cystic kidney in tuberous sclerosis, and in von Hippel-Lindau syndrome, cystic nephroma, cystic variant of congenital mesoblastic nephroma, mixed epithelial stromal tumor of the kidney, renal lymphangioma, pyelocalyceal cyst, peripylic cyst and perinephric pseudocyst, acquired renal cystic disease of long-term dialysis, and cystic renal cell carcinoma and sarcoma. Whereas the gross and histologic appearance of some of these conditions may be diagnostic, clinical and sometimes molecular studies may be necessary to define other types.     

Histologic and fine-needle aspiration cytologic features of polycystic disease of the parotid glands: case report and review of the literature

Polycystic disease of the parotid glands is a rare disorder, with only eight examples to our knowledge being reported in the literature. The disease presents as a painless enlargement of one or both parotid glands and does not appear to be associated with other disease processes within the head and neck, or with polycystic disease of the kidney, pancreas, or congenital fibrosis of the liver. The histology has been well described. The overall glandular architecture is preserved but the lobules are markedly distended by cysts whose lining appears to be intercalated duct in differentiation. Characteristic eosinophilic laminated spheroliths lie in many of the cystic spaces. Aspirate smears are characterized by a relatively clean background in which are distributed histiocytes, red blood cells, and small clusters of ductal epithelial cells. Polycystic disease of the parotid glands must be differentiated cytologically from mucous retention reaction, mucoceles, benign lymphoepithelial cysts, and cystic neoplasms, including Warthin's tumor, low-grade mucoepidermoid carcinoma, cystadenoma, and papillary cystadenocarcinoma.     

Alveolar adenoma of the lung

Solitary coin lesions in the lung invoke an expanding differential diagnosis and while pulmonary hamartoma and a neuroendocrine tumour are the commonest causes, there are other lesions that need to be considered. Alveolar adenoma and sclerosing pneumocytoma are two such lesions.This is a case of an alveolar adenoma in a 41-year-old asymptomatic female who was found to have a peripheral solitary lesion on routine chest X-ray. In view of suspicious cytology, she had a left lower lobectomy. The lesion was well-circumscribed and composed of multiple cystic structures of varying size. The cysts were lined by epithelial cells ranging from flat to cuboidal to hobnail, and conformed to type II pneumocytes. The stroma between the cysts contained bland spindle shaped cells and mixed inflammation, including several mast cells. Immunohistochemistry showed the cyst lining cells to be positive for epithelial markers and TTF-1. The stromal cells were negative for these stains.Alveolar adenoma is a rare benign cystic neoplasm of lung with a superficial resemblance to a lymphangioma and is thought to arise from type II pneumocytes.     

Atypical epithelial proliferations in acquired renal cystic disease harbor cytogenetic aberrations

Acquired renal cystic disease (ARCD) complicating end-stage renal failure confers an increased risk for renal cell carcinoma, and atypical epithelial proliferation in the cysts may represent the precursor lesion. In this report we used an interphase cytogenetic technique to analyze the karyotypic features of various forms of atypical epithelial proliferations in a patient with ARCD. Both kidneys harbored numerous simple and atypical cysts. In addition, papillary tufts and a hitherto undescribed cribriform epithelial proliferation were found in the right kidney. The left kidney contained a 10-mm renal cell carcinoma with features indeterminate between clear cell and papillary types. There was gain of chromosome 7 in the papillary tufts; gain of chromosomes 7 and 17 in the cribriform lesion; gain of chromosomes 7, 12, 17, 20, and Y in the atypical cysts; and gain of chromosomes 7, 12, 17, and 20 in the renal cell carcinoma. These chromosomal aberrations suggest that atypical epithelial proliferations in ARCD represent early neoplastic lesions.     

Renal lesions in von Hippel-Lindau disease: immunohistochemical expression of nephron differentiation molecules, adhesion molecules and apoptosis proteins

AIMS: Renal lesions in von Hippel-Lindau disease comprise clear cell simple cysts, atypical cysts and carcinomas. Although histological and molecular studies suggest that cystic lesions may represent precursors of carcinomas, there is no detailed phenotypic evidence of their relationship. METHODS AND RESULTS: To investigate such a possible relationship between cystic lesions and solid carcinomas, we studied the pathological and immunohistochemical features of 328 lesions of 33 kidneys originating from 23 patients with von Hippel-Lindau disease, using a panel of antibodies directed against cytoskeleton proteins, cell surface proteins, integrin subunits, adhesion molecules, lectins, and apoptosis and proliferation markers. Solid carcinomas (n = 175) were all of clear cell type and mostly nuclear grade 1. Cystic lesions (n = 138) consisted of cystic clear cell carcinomas (n = 15), atypical cysts (n = 20) and simple cysts (n = 103). Clear cells of the simple cysts, atypical cysts and solid carcinomas coexpressed cytokeratins (CK8, CK19) and vimentin, and expressed a similar pattern of tubular markers (CD24, tetraglonolobus), integrin subunits (alpha3, alpha5, alpha6, alphav, beta1) and cell adhesion molecules (ICAM 1, VCAM 1). In all lesions studied, proliferation rate (MIB1 index) was low, and apoptosis marker expression (fragmented DNA, p53, bcl-2) inconspicuous. CONCLUSIONS: Phenotypic alterations found in solid renal cell carcinomas are already present in simple and atypical renal cysts of von Hippel-Lindau disease.