Adenocarcinoma of the colon simulating primary urinary bladder neoplasia. A report of nine cases.

Nine cases of adenocarcinoma of the colon, secondarily involving the urinary bladder mucosa and histologically mimicking primary bladder neoplasia, are reported. Five patients presented with bladder involvement at the time of diagnosis of colon cancer; four developed vesical lesions 9 to 66 months after resection of their colonic primary. The majority (89%) had genitourinary symptoms at presentation; gastrointestinal manifestations were present in only 60% of those with synchronous colonic involvement. The initial clinical impression, largely based on cystoscopic and radiographic studies, was a bladder primary in four cases and colon cancer in five. Of the former, three (75%) were known to have a history of colon cancer. Histologically, all were enteric-type adenocarcinomas and all had features mimicking a villous adenoma of the bladder. Distinguishing a primary bladder adenocarcinoma from spread of a colonic carcinoma to the bladder may not be possible on histopathologic grounds alone. Consideration should be given to the possibility of an extravesical primary even when symptomatology, cystoscopy, radiographic studies, and histopathology suggest a primary bladder neoplasm.

Primary osteogenic sarcoma of the breast: a clinicopathologic analysis of 50 cases.

Extraskeletal osteosarcomas are rare. Few primary mammary osteosarcomas have been reported; many of these have been described in association with a biphasic tumor. Fifty pure osteosarcomas of the breast, diagnosed between 1957 and 1995, were reviewed after excluding those of biphasic origin. The absence of epithelial differentiation was confirmed using a panel of immunohistochemical markers in 32 cases and using ultrastructural evaluation in an additional four cases. Tumors occurred in 49 women and one man; age ranged from 27 to 89 years (median, 64.5 years). One patient received radiotherapy for ipsilateral breast carcinoma 9 years before presentation. Patients were treated by excisional biopsy (n = 13), tylectomy (n = 5) or mastectomy (n = 32). All axillary nodes, dissected in 20 patients, were free of tumor. One patient had extramammary spread at diagnosis. The neoplasms were 1.4 cm to 13.0 cm (mean, 4.6 cm), and 60% were grossly circumscribed. Tumors were classified as fibroblastic (n = 28), osteoclastic (n = 14), or osteoblastic (n = 8). Of 39 patients with available follow-up information, locally recurrent (n = 11) and metastatic (n = 15) disease developed in 23 (59%) at a mean of 10.5 and 14.5 months from diagnosis. Eight (73%) patients in whom local recurrence developed were treated with excisional biopsy or tylectomy; of these, seven had a positive margin. Sixteen (41%) patients died of disease at a mean of 17.1 months, within 20 months of onset of metastases, most commonly to the lung. Mammary osteosarcomas are aggressive tumors with a propensity for blood-borne rather than lymphatic spread. Total excision without axillary dissection is advised.

True papillary carcinoma of the lung: a distinct clinicopathologic entity.

There continues to be confusion as to whether papillary adenocarcinoma (PA) of the lung is a specific histologic entity or simply a variant of bronchioloalveolar carcinoma (BAC). We reviewed our files from 1981 through 1993 for all cases (n = 155) of resected primary lung adenocarcinoma specifically diagnosed as having papillary or bronchioloalveolar features. In addition, a random 10% (n = 67) of all remaining lung adenocarcinomas were reviewed. True PA was diagnosed when > or = 75% of the neoplasm contained papillary structures supported by fibrovascular cores with complicated secondary and tertiary branches. Marked nuclear atypia was present in 100%, and psammoma bodies were seen in 42% of cases. In contrast to BAC, true PA filled and distorted or replaced air spaces in the lung. Thirty-one cases of true PA were found, including 19 men and 12 women (mean age, 64.5 years). The lesions were solitary (n = 27) or multifocal (n = 4) with a mean diameter of 4.1 cm. Forty-five percent of patients had bronchopulmonary lymph node involvement at diagnosis; another 10% had extensive intrapulmonary lymphatic permeation by tumor. Disease-free survival for stage I and II PA was 40% (n = 15) and 25% (n = 8), respectively, at a mean of 3.4 and 3.5 years. Papillary adenocarcinoma of the lung is a distinct clinicopathologic entity with considerably worse morbidity and mortality than BAC.

Osteosarcomatous differentiation in phyllodes tumors.

Osteosarcomatous differentiation in phyllodes tumors is uncommon. The clinicopathologic features of 22 such cases in our files were retrospectively reviewed to evaluate the prognostic significance of this rare neoplasm. All patients were women between 40 and 83 years of age (mean, 60 years). Most (73%) presented with a palpable mass. None had prior irradiation to the breast or chest region. Patients were treated with excisional biopsy (N = 4), partial mastectomy (N = 1), or mastectomy (N = 17). All axillary nodes, dissected in 11 patients, were free of tumor. Two patients had extramammary spread at diagnosis. The neoplasms measured 1.9-15 cm (mean, 6.4 cm); 54% were grossly circumscribed or multilobulated. The osteosarcomatous component was classified as fibroblastic (N = 11), osteoclastic (N = 6), or osteoblastic (N = 5) and occupied a variable percentage of the phyllodes' stroma ranging from -25% to essentially 100% of the neoplasm. Of 21 patients with available follow-up, 11 (52%) were alive at a median follow-up of 44 months. Nine patients (43%) developed locally recurrent (N = 1) or metastatic (N = 8) disease. Metastases were clinically apparent within 1 year of diagnosis in all eight patients; seven died within 12 months of detection of initial metastasis. By univariate analysis, gross tumor size and osteosarcoma subtype significantly correlated with prognosis. In a multivariate analysis, neither of these factors were independent prognosticators. Phyllodes tumors with an osteosarcomatous component are potentially aggressive neoplasms, particularly when large (>5 cm) or associated with an osteoclastic or osteoblastic osteosarcoma. Complete excision without axillary dissection is advised.

Mesonephric adenocarcinomas of the uterine cervix: a study of 11 cases with immunohistochemical findings.

Mesonephric adenocarcinoma is a rare variant of cervical carcinoma with relatively few, well-documented cases reported. We describe the clinicopathologic and immunohistochemical features of 11 examples of this neoplasm, which occurred in women between the ages of 35 and 72 years (mean, 52 years). Most (64%) patients had abnormal vaginal bleeding. Eight tumors were stage IB, and one each was stage IIB and IVB; in one, the stage was unknown. Microscopically, the carcinomas showed various morphologies, most commonly a small tubular pattern or a ductal pattern resembling endometrioid adenocarcinoma; one tumor had an associated malignant spindle cell component. Ten neoplasms were adjacent to hyperplastic mesonephric remnants. Follow-up in 10 cases showed six patients to be alive without evidence of recurrence after a mean of 4.8 years. The patients with stage IIB and IVB disease had local recurrences after 2.2 and 0.7 years and died of progressive disease at 3.2 and 0.8 years, respectively. In a patient with stage IB disease, a mediastinal metastasis and a malignant pleural effusion developed 5.6 years after diagnosis, and the patient died of disease at 6.2 years. Another patient with stage IB disease and a positive vaginal cuff margin that recurred locally after 1.7 years received chemotherapy and was alive and clinically free of disease at 2.5 years. Mesonephric adenocarcinomas were immunoreactive for epithelial markers (AE1/3; CK1, CAM 5.2, cytokeratin 7, and epithelial membrane antigen) (100%), calretinin (88%), vimentin (70%), androgen receptor (33%), and inhibin (30%, focal staining). No immunostaining was detected with cytokeratin 20, estrogen receptor, progesterone receptor, and monoclonal carcinoembryonic antigen. This staining profile is similar to that of mesonephric remnants and may be useful in the distinction of mesonephric carcinoma from mullerian endometrioid adenocarcinoma, with which it may be confused.

Composite cytological smears of pelvic lymph nodes at the time of radical prostatectomy to identify nodal metastases.

Many urologists will abort a radical prostatectomy (RP) after intraoperative identification of regional lymph node (LN) metastases because RP in these patients is not curative. Because frozen section techniques are time consuming and incompletely sample LNs, we evaluated the efficacy of performing a composite cytological smear (CCS) by sampling all grossly identifiable LNs. Two hundred and fifty RPs performed from November 1991 to June 1992 yielded on permanent section 33 (+) pelvic lymph node dissections (PLNDs) (6.6%) in 25 RPs (10%). Eleven (33%) of the 33 PLNDs with metastases were grossly suspicious, all were identified by CCS (median percentage of positive LNs per PLND = 33; median size of the largest metastasis = 11 mm). Of the remaining 22 grossly negative PLNDs with tumor, only seven (32%) were detected by CCS (median percentage of positive LNs per PLND = 13; median size of largest metastasis = 3 mm). In the 15 cases missed by CCS the median percentage of positive LNs per PLND was 14, and the median size of the largest metastasis was 1 mm. This method reliably detected LN metastases measuring more than 2 mm as long as the positive LN was grossly recognizable as an LN and thus sampled by CCS. In conclusion, CCS is highly specific but insensitive for the detection of limited numbers of micrometastases, which are the most common type of metastases in patients with low clinical stage disease. A combined technique employing frozen sections on smaller nodes and CCS on larger nodes may be more effective in identifying small metastatic deposits.

Wolffian adnexal tumor, so-called female adnexal tumor of probable Wolffian origin (FATWO): immunohistochemical evidence in support of a Wolffian origin.

Wolffian adnexal tumor (WAT) is a rare neoplasm believed to originate from wolffian remnants on the basis of its location in areas where these remnants are abundant. To study its histogenesis, the immunoprofile of 25 WATs was compared with that of 10 cervical and vaginal mesonephric remnants and 12 rete ovarii. WATs were unilaterally located in the broad ligament (n = 10), mesosalpinx (n = 9), ovarian hilus (n = 5), and pelvis, not otherwise specified (n = 1). They showed varying morphologies with solid (spindle cells), tubular (lined by columnar cells), retiform and multicystic (spaces lined by cuboidal and attenuated cells) patterns. WATs were immunoreactive for pan-cytokeratin (AE1/3, CK1) (100%), CAM 5.2 (100%), cytokeratin 7 (CK7) (88%, focal staining), keratin 903 (17%), epithelial membrane antigen (EMA) (12%), estrogen receptor (28%), progesterone receptor (24%), androgen receptor (78%), inhibin (68%), calretinin (91%), and vimentin (100%). No immunostaining was detected with monoclonal carcinoembryonic antigen and cytokeratin 20. The pattern of staining was nearly identical to that of the rete ovarii and differed somewhat from mesonephric remnants, which were diffusely immunoreactive for CK7, immunopositive for EMA (apical staining), and nonreactive for inhibin. Our findings provide immunohistochemical support for the derivation of WATs from wolffian remnants, in particular from the rete ovarii. Because of immunoreactivity for inhibin and calretinin in a significant number of WATs, our results further show that these immunostains alone do not allow absolute distinction of WATs from sex cord-stromal tumors and adenomatoid tumors, respectively, with which they may be confused.

Loss of retinoblastoma gene function and heterozygosity at the RB locus in renal cortical neoplasms.

Alteration of the retinoblastoma (RB) gene, located on chromosome 13q14, has been implicated in the pathogenesis and biological behavior of several human cancers. We investigated the RB gene status by Western blotting and immunohistochemical analysis, as well as loss of heterozygosity (LOH) at the RB locus in 21 primary human renal neoplasms (including 3 oncocytomas). In only 1 of 21 tumors was there a discrepancy between Western blot and immunochemical staining. Overall, LOH was noted in 6 of 12 informative cases. However, only one of the tumors with LOH at the RB locus had loss of RB protein expression by both Western blot and immunohistochemical analysis. Loss of RB function was found in 4 of 18 carcinomas and in none of 3 oncocytomas as determined by absent RB nuclear staining in tumor cells. LOH at chromosome 13q14 was more noted in high-grade, DNA aneuploid, high-stage tumors and in patients with poor outcome. These results imply that (1) there is likely another tumor-suppressor gene on chromosome 13 involved in renal carcinogenesis, (2) LOH at chromosome 13q loci may be associated with aggressive behavior, and (3) the loss of RB function may have a role in a subset of renal carcinomas.

Glomus tumor arising in a mature teratoma of the ovary: report of a case simulating a metastasis from cervical squamous carcinoma.

Glomus tumors involving the female genital tract are rare. Herein we report the case of a glomus tumor constituting the major component of a mature teratoma of the ovary. This lesion represented an incidental finding in a 43-year-old woman who underwent bilateral salpingo-oophorectomy at the time of detection of locally recurrent squamous carcinoma of the cervix. The glomus tumor was initially interpreted as a metastasis due to its superficial morphologic resemblance to the recurrent carcinoma in the vagina. It was, however, morphologically similar to glomus tumors that classically arise in the extremities. The diagnosis was supported by immunohistochemistry and ultrastructural examination. To our knowledge, no similar tumor has been described in the ovary or in teratomas at any other site.

Cerebral cysticercosis mimicking malignant glioma: a case report.

BACKGROUND: Cysticercosis is the most common parasitic infection of the central nervous system in the United States. CASE: A case of cerebral cysticercosis radiographically and pathologically mimicked a high grade glioma. A symptomatic solitary cerebral hemispheric lesion in a child, unknown at the time to have been born in Korea and adopted by U.S. residents, was initially evaluated by stereotactically guided needle biopsy and diagnosed as having malignant glioma in accord with the radiographic impression. The subsequently excised mass revealed cysticercus with an exuberant granulomatous inflammation and gliosis surrounding a fibrous-walled cyst. CONCLUSION: In the setting of a solitary parenchymal cyst, the radiographic differential diagnosis of neurocysticercosis often includes a primary neoplasm. However, to our knowledge, this is the first report of cysticercosis's also simulating a brain neoplasm pathologically.

Diagnosis of progressive multifocal leukoencephalopathy by stereotactic brain biopsy utilizing immunohistochemistry and the polymerase chain reaction.

This report describes the diagnosis of progressive multifocal leukoencephalopathy (PML) in nine patients using cytopathologic and histopathologic examination of computed tomographically guided stereotactic brain biopsies in combination with immunostaining for SV-40-related antigen and the polymerase chain reaction (PCR) for the JC virus. In four patients the diagnosis of PML was based on the microscopic appearance of the biopsies and immunostaining for SV-40-related antigen. In one of these patients the diagnosis was also supported by PCR for the JC virus. In two patients whose biopsies were only suggestive of PML, a definitive diagnosis was possible utilizing immunohistochemistry and PCR. In another case the histopathologic features were atypical of PML, and the diagnosis was established with immunostaining and PCR. The diagnosis of PML was established by PCR alone in two patients whose biopsies showed only suggestive or nonspecific findings. We conclude that the accuracy of stereotactic biopsy in the diagnosis of PML is enhanced by using a combination of light microscopy, immunohistochemistry and PCR.

Pleomorphic carcinoma of the breast: clinicopathological analysis of 26 cases of an unusual high-grade phenotype of ductal carcinoma.

AIMS: Pleomorphic carcinoma is a poorly described entity whose phenotype is not well recognized as within the morphological spectrum of breast carcinoma. The purpose of this report is to describe the clinicopathological features of this tumour, and to promote its recognition as an unusual high-grade morphological variant of mammary ductal carcinoma. METHODS AND RESULTS: Histological slides of breast carcinomas (N = 64) coded between 1978 and 1995 as having pleomorphic or anaplastic features were reviewed. Pleomorphic carcinoma (N = 26) was diagnosed when > or = 50% of the tumour manifested a pleomorphic cell population (> sixfold variation in nuclear size). Tumours of lobular origin were excluded. All neoplasms occurred in women with a mean age of 53 years. Patients underwent biopsy and/or mastectomy (n = 24) or lumpectomy (n = 2). The tumours' mean size was 54 mm. All were high-grade neoplasms. The pleomorphic cell population comprised 50-100% of the tumour; 31% had a prominent spindled morphology. Fifty-eight per cent of the tumours were initially misclassified by referring pathologists as sarcomas or carcinomas, possibly metastatic. Adjacent DCIS or a transition to classic ductal carcinoma was present in 73%. Five (19%) patients were stage I and three (12%) had stage IV disease. Axillary dissections yielded > or = 3 (mean 7.2) positive lymph nodes in 52%. Most (68%) tumours were aneuploid; a high S-phase (> 10%) was present in 63%. All neoplasms were ER negative and all but one were PR negative. p53 expression was present in 71%; none expressed bcl-2. c-erbB-2 was detected in four (19%) node-positive and in 0 (0%) node-negative cases (P = 0.01). Of 16 patients with follow-up, 6 (38%) were disease-free (mean, 74 months), four (25%) alive with disease (mean, 33 months) and six (38%) dead of disease at a mean of 22 months. CONCLUSIONS: Pleomorphic carcinoma is a prognostically unfavourable lesion and represents the extreme end of the morphological spectrum of grade III infiltrating ductal carcinoma.

Morphologic and immunophenotypic characterization of foam cells in endometrial lesions.

The detection of foam cells in cervicovaginal smears obtained from postmenopausal women suggests the possibility of an endometrial lesion. Ultrastructural studies have suggested that foam cells represent endometrial stromal cells but the histogenesis of these cells has not been firmly established. To investigate the origin and diagnostic significance of foam cells, we analyzed the morphology and immunophenotype of these cells in endometrial tissue specimens and correlated the findings with cervical smears obtained within the preceding 6 months. Selected biopsies containing foam cells were evaluated using four well-characterized macrophage markers: KP-1(CD68), HAM 56, MAC 387, and lysozyme. Foam cells were found in 11 (38%) of 29 simple hyperplasias, 7 (50%) of 14 complex hyperplasias, 6 (50%) of 12 complex atypical hyperplasias, 21 (70%) of 30 adenocarcinomas, 1 (4%) of 25 samples with stromal breakdown, and 0 of 30 specimens showing normal cycling endometrium. Foam cells were also found in smears preceding the histologic diagnosis of 2 (13%) simple hyperplasias, 2 (25%) complex hyperplasias, 3 (43%) complex atypical hyperplasias, 5 (28%) adenocarcinomas, 5 (28%) cases of stromal breakdown, and 0 of 8 normal tissue specimens examined. Foam cells were immunoreactive with at least 2 of the 3 macrophage-specific antibodies in all 21 biopsies studied. Our results suggest that foam cells phenotypically represent macrophages and not endometrial stromal cells. Foam cells are identified in a significant percentage of cervical smears and endometrial tissue specimens obtained from women with endometrial pathology. The morphology and immunophenotype of foam cells, however, does not appear to be useful in distinguishing benign endometrial stromal breakdown, endometrial hyperplasia, and endometrial adenocarcinoma.

Mammary ductal carcinoma in situ with microinvasion.

BACKGROUND: The natural history of patients with intraductal carcinoma (DCIS) and microinvasion is poorly defined, and the clinical management of these patients, with particular reference to management of the axilla, has been controversial. Previous studies of this lesion have used varied and/or arbitrary criteria for the evaluation of microinvasion. METHODS: Thirty-eight DCIS lesions with microinvasion (n=29) or probable microinvasion (n=9), diagnosed during the period 1980-1996, were retrospectively analyzed after cases not treated with mastectomy and axillary lymph node dissection were excluded. Microinvasion was defined as a single focus of invasive carcinoma < or = 2 mm or up to 3 foci of invasion, each < or =1 mm in greatest dimension. RESULTS: The patients were all females with a mean age of 56.4 years. DCIS was of comedo (n=31) or papillary (n=7) subtype. Microinvasion was often associated with an altered, desmoplastic stroma (55%) or a lymphocytic infiltrate (39%). The foci of microinvasion ranged from 0.25 to 1.75 mm (mean, 0.6 mm), with an aggregate mean size of 1.1 mm (range, 0.25-2.25 mm). Foci of microinvasion, ranging from 1 to 3 (mean, 1.7), were adjacent to DCIS in 95.3% of cases. The extent of DCIS did not correlate with the number of foci of microinvasion. Axillary lymph node dissections yielded a mean of 19.3 lymph nodes (range, 7-38), and all lymph nodes were negative for metastasis. None of 33 patients, followed for a mean of 7.5 years (range, 1.0-14.4 years), developed local recurrence or metastasis. CONCLUSIONS: The cases of microinvasive carcinoma examined in this study, as defined above, were not associated with axillary lymph node metastases and appeared to be associated with an excellent prognosis. Further study is indicated to determine the appropriate management and long term prognosis of patients with this lesion.

DNA ploidy analysis of pediatric germ cell tumors.

To determine the usefulness of DNA ploidy analysis in the biological assessment of pediatric germ cell tumors (GCTs), paraffin-embedded tissues from primary, recurrent, and metastatic neoplasms in 32 patients under age 18 were analyzed using static image cytometry. Primary sites included testis (eight), ovary (nine), sacrococcygeal region (10), central nervous system (three), and other extragonadal sites (two). The majority of the tumors were endodermal sinus tumors (ESTs) and teratomas. Of 13 teratomas, eight were diploid and five aneuploid. Immature ovarian teratomas of up to Grade II were diploid, whereas all of three Grade III immature teratomas were aneuploid. All sacrococcygeal teratomas, regardless of grade, were diploid; the development of EST in two sacrococcygeal teratomas was associated with the development of aneuploidy. Of 17 endodermal sinus tumors, five were diploid, five aneuploid, and seven tetraploid. All diploid ESTs occurred in the testis or extragonadally in patients 24 mo of age or younger. Infantile testicular ESTs were either tetraploid (one) or diploid (two), and ovarian ESTs were either aneuploid (two) or tetraploid (three). Comparing our data with that available for adult GCTs, we suggest that some pediatric GCTs may be pathogenetically distinct from adult GCTs. Adult testicular GCTs have been shown to be aneuploid, whereas infantile testicular ESTs are often tetraploid or diploid. This suggests a different pathogenesis for these groups of tumors and may explain their biological differences as well. The transformation of a sacrococcygeal teratoma into a malignant EST is poorly understood. Ploidy analysis presented suggests genetic alterations may accompany this transformation.

Factors influencing hydrocarbon degradation in three freshwater lakes.

The mixed microbial flora of 3 lakes in Ohio with differing histories of hydrocarbon pollution was examined in relation to the ability to use hydrocarbons. Weathered kerosene was spiked with naphthalene, pristane, 1,13-tetradecadiene, andn-hexadecane and added to water-sediment mixtures from the 3 lakes, and utilization of the 4 marker hydrocarbons was measured. Each of the marker hydrocarbons was metabolized; naphthalene was the most readily used and pristane was the most resistant. Values for dissolved oxygen suggest that oxygen did not limit hydrocarbon degradation in the water column at any site examined. Nutrient addition studies indicated that nitrogen and phosphorus limited hydrocarbon degradation at all sites examined. Maximum numbers of heterotrophic bacteria were detected when the water temperature was 10°C or higher. The data indicate that temperature limits hydrocarbon degradation in the winter, except at a site which had been impacted by an oil spill and which received chronic inputs of hydrocarbons and nutrients. In samples from that site, all 4 marker hydrocarbons were degraded at 0°C. Results of temperature and nutrient-addition experiments suggest that different seasonal populations of hydrocarbon users are selected at that site, but not at other lake sites.

Oncocytic metaplasia and carcinoma of the endometrium: an immunohistochemical and ultrastructural study.

Endometrial oncocytic carcinoma is an unusual neoplasm, with few cases reported. Endometrial curettage specimens coded as prominent oxyphilic metaplasia (N = 5) and oxyphilic or oncocytic carcinoma (N = 4) were reviewed, and hysterectomy slides from the four carcinomas were also examined. Immunohistochemical and ultrastructural analyses were performed in three of five metaplasias and in all four carcinomas. Most patients (89%) with oncocytic metaplasia and carcinoma had vaginal bleeding. Oncocytic metaplasia was characterized by a single layer of cells with abundant eosinophilic, granular cytoplasm, minimal pleomorphism, and rare mitotic activity. Carcinoma was diagnosed on the basis of an altered stroma (n = 2) and/or a confluent growth pattern (n = 4) and had a papillary (n = 4), glandular (n = 2), or solid (n = 1) morphology. Carcinomas showed a similar population of oncocytic cells as metaplasias, but with occasional nuclear stratification and greater pleomorphism and mitotic activity. Tumors were International Federation of Gynecology and Obstetrics (FIGO) grade 1 (n = 2) or 2 (n = 2) and FIGO stage Ib, Ic, IIb, and IIIc. Omental metastases developed in the patient with the stage III tumor at 13 months; the two patients with stage I tumors were alive with no evidence of disease at a mean of 29 months. All carcinomas expressed p53 and 75% and 100% were estrogen receptor (ER)- and progesterone receptor (PR)-negative, respectively, whereas all metaplasias were p53 negative- and ER- and PR-positive. Ki-67 labeling index was 1 to 3% in metaplasias and 14 to 33% in carcinomas. Oncocytic metaplasias and carcinomas contained abundant mitochondria and free ribosomes, accounting for the oncocytic appearance. Because oncocytic carcinomas frequently show deep myometrial invasion and require surgical staging, it is important to distinguish oncocytic metaplasia from carcinoma on biopsy material. Ki-67, p53, and ER and PR immunostains may assist in this potentially difficult differential.