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K A Iczkowski

Publications and source records attributed to K A Iczkowski.

At least 19 recordsLinked to original sources
PubMed2006

Adenoid cystic/basal cell carcinoma of the prostate strongly expresses HER-2/neu.

Adenoid cystic/basal cell carcinoma (ACBCC) is a rare neoplasm in the prostate. Definitive treatment is warranted, as among 19 patients previously reported by us, 5 had extraprostatic extension and 4 were metastatic. The HER-2/neu (c-erbB-2) gene has been reportedly overexpressed in adenoid cystic carcinomas in other organs, but its status in prostatic ACBCC was uncertain. Immunohistochemical staining and in situ hybridisation were carried out in 13 patients with ACBCC (11 from transurethral resection, 2 prostatectomy). One patient had metastasis to the lung. Citrate buffer and steam heat were used for antigen retrieval. Ten acinar adenocarcinomas of varying grades were also immunostained as controls. Protein and mRNA expression were 2+ to 3+ (of 3+) in all patients with ACBCC, compared to a breast cancer control with strong reactivity, whereas protein expression was noted in only one acinar carcinoma and mRNA expression was absent in all acinar carcinomas. Benign acini expressed HER-2/neu only in the basal layer. The finding of strong, consistent HER-2/neu expression in ACBCC suggests that treatment with Herceptin (trastuzumab) may be effective in patients with this rare tumour.

Adult↗
PubMed2004

Alpha-methylacyl-CoA racemase: a multi-institutional study of a new prostate cancer marker.

AIM: To test whether alpha-methylacyl-CoA racemase (AMACR) is a sensitive and specific marker of prostate cancer. METHODS AND RESULTS: The expression levels of AMACR mRNA were measured by real-time polymerase chain reaction. A total of 807 prostatic specimens were further examined by immunohistochemistry specific for AMACR. Quantitative immunostaining analyses were carried out by using the ChromaVision Automated Cellular Imaging System and the Ariol SL-50 Imaging System, respectively. AMACR mRNA levels measured in prostatic adenocarcinoma were 55 times higher than those in benign prostate tissue. Of 454 cases of prostatic adenocarcinoma, 441 were positive for AMACR, while 254 of 277 cases of benign prostate were negative for AMACR. The sensitivity and specificity of AMACR immunodetection of prostatic adenocarcinomas were 97% and 92%, respectively. Both positive and negative predictive values were 95%. By automatic imaging analyses, the AMACR immunostaining intensity and percentage in prostatic adenocarcinomas were also significantly higher than those in benign prostatic tissue (105.9 versus 16.1 for intensity, 45.7% versus 0.02% and 35.03% versus 4.64% for percentage, respectively). CONCLUSIONS: We have demonstrated the promising features of AMACR as a biomarker for prostate cancer in this large series and the potential to develop automated quantitative diagnostic tests.

Adenocarcinoma↗
PubMed2001

Inflammatory pseudotumor and sarcoma of urinary bladder: differential diagnosis and outcome in thirty-eight spindle cell neoplasms.

We assessed diagnostic criteria among 38 spindle cell tumors of the urinary bladder and obtained follow-up in 36 patients. Patients comprised 28 males and 10 females aged 2.5 months to 87 years. Hematuria was the commonest presenting symptom (27 patients). After review and immunohistochemical workup, 17 patients had inflammatory pseudotumor (myofibroblastic tumor), 4 postoperative spindle cell nodule, 1 leiomyoma, 13 sarcoma (7 low-grade; 6 high-grade), and 3 carcinoma. Mean age was 38 years for pseudotumor (range 15 to 74), 65 for postoperative spindle cell nodule, 51 for sarcoma, and 76 for carcinoma. Size of pseudotumor averaged 4.4 +/- 0.7 cm (range 1.5 to 13.0), similar to sarcoma, 4.0 +/- 0.6 cm (range 0.5 to 7.0). Similar proportions of benign tumors and sarcomas had muscularis propria invasion. The criteria that best differentiated sarcoma from inflammatory pseudotumor were presence of necrosis at the tumor-detrusor muscle interface in muscle-invasive cases, and nuclear atypia. Sarcoma also had less prominent microvasculature, less variable cellularity, consistently > or =1 mitotic figure per 10 high-power fields, and predominant acute inflammation without plasma cells. p53 protein nuclear immunostaining was moderate, unlike the rare to absent staining in pseudotumors. Because all 12 sarcomas were desmin-negative, we did not call them leiomyosarcoma; they overlapped with benign tumor in epithelial, mesenchymal, and actin immunostaining. Among 12 sarcoma patients, 2 died of tumor (at 3 months). Two of four experienced tumor recurrence after partial cystectomy (2 and 26 months). No pseudotumors recurred after transurethral resection or partial cystectomy, although one patient, 5 months after transurethral resection, had histologically identical pseudotumor that the surgeon considered residual. Another patient with pseudotumor, not a candidate for tumor ablation after transurethral resection, had continued tumor growth and he died of urosepsis. In conclusion, inflammatory pseudotumor, although overlapping with sarcoma in presentation, age range, and size, does not metastasize and remains histologically distinct from low-grade sarcoma.

Actins↗
PubMed2001

CD44s expression is reduced in endometriotic lesions compared to eutopic endometrium in women with endometriosis.

Immunohistochemical expression of the standard form of CD44 (CD44s) was examined in archival formalin-fixed endometriotic and matching eutopic endometrial tissue obtained from 25 patients in proliferative (N = 16) and secretory (N = 9) stages of the cycle. CD44s was expressed in most eutopic endometria and endometriotic tissue. Its expression was significantly higher in secretory than in proliferative phase endometrium. It was low but detectable in 13 of 16 proliferative phase biopsies. The majority of these endometria exhibited both glandular and stromal staining (63%). In the secretory phase, glandular cells exhibited a significantly greater intensity of staining compared to stromal cells. In endometriotic tissue, stromal cell CD44s expression did not differ between tissue types in either stage of the cycle. In contrast, glandular expression in endometriotic tissue during the secretory phase was reduced (p < 0.05) compared to eutopic endometrium. It was absent in 66% of cases and reduced in the remaining cases. Our results indicate a correlation between CD44s expression and secretory differentiation of endometrial glands in the cycle, suggesting hormonal regulation of its expression. This cyclic pattern of CD44s expression was lost in corresponding endometriotic tissue. Reduced expression of CD44s in endometriotic tissue may provide insight into the pathophysiology of endometriosis.

Adult↗
PubMed2000

Sampling, submission, and report format for multiple prostate biopsies: a 1999 survey.

OBJECTIVES: Much variation occurs in sampling, submission, and reporting of prostate biopsies. Current practice standards among physicians across the United States are uncertain. METHODS: We surveyed predominantly nonacademic urologists and pathologists. The response rate was 57 (21%) of 271 urologists and 47 (55%) of 85 pathologists. RESULTS: Fifty-five percent of urologists performed six (or more) site-designated biopsies; 41% used unspecified bilateral biopsies. More than one half of urologists and pathologists reported submitting or receiving six or more separate, site-designated containers. The remainder of physicians (less than one half) reported the submission of all left needle cores in one container and all right cores in the other. Most pathologists (70%) stated that billing depended on the number of containers; 15% were unsure. One hundred percent of academic and 68% of nonacademic urologists deemed the report format therapeutically relevant (P <0.03), as did 57% of pathologists. Physicians submitting or receiving sextant needle biopsies in separate containers shared a 3:1 preference for issuance of a separate line diagnosis for each sextant site instead of condensing all diagnoses into one line with one Gleason score. Similarly, for each biopsy site, 61% of urologists wanted a separate Gleason score, and 68% wanted a separate designation for the percentage of tissue with tumor. Fifty-six percent and 64% of urologists and pathologists, respectively, deemed it relevant to specify the site(s) of high-grade prostatic intraepithelial neoplasia, even if cancer were present. CONCLUSIONS: Much variation persists in prostate biopsy sampling and reporting, hindering communication among physicians from different institutions. However, similar percentages of urologists and pathologists reported separate versus combined site sampling and separate versus combined site report format preferences.

Adenocarcinoma↗
PubMed2000

Cytokeratin expression in seminoma of the human testis.

We studied cytokeratin (CK) expression immunohistochemically in 64 seminomas using a panel of commercially available antikeratin antibodies and tested for association of CK expression with patient age, tumor size, stage, and outcome. Seventeen embryonal carcinomas were compared with seminoma. CK7, CAM 5.2, AEI/AEIII, and wide-spectrum screening keratin (WSK) were positive in 41%, 30%, 36%, and 36% of the seminomas, respectively. CK20 and high-molecular-weight keratin (HMWK) were negative in all cases. CD30, placental alkaline phosphatase (PLAP), and epithelial membrane antigen (EMA) were positive in 6%, 100%, and 2% of cases, respectively. There were no differences in patient age, stage, tumor size, or outcome between CK-positive and CK-negative seminomas. CK7, CAM 5.2, AEI/AEIII, and WSK were positive in 100%, 88%, 94%, and 88% of embryonal carcinomas, respectively. CK20 and HMWK were negative in all cases. CD30, EMA, and PLAP were positive in 100%, 12%, and 76%, respectively. CKs are present in seminoma, and their presence is not associated with a difference in patient age, stage, or outcome. In cases such as small needle biopsy specimens, CK and CD30 stains may be useful in separating seminoma from embryonal carcinoma.

Adult↗
PubMed2000

Criteria for biopsy diagnosis of minimal volume prostatic adenocarcinoma: analytic comparison with nondiagnostic but suspicious atypical small acinar proliferation.

CONTEXT: Minimal volume prostatic adenocarcinoma (defined as involving less than 5% of biopsy tissue) is diagnosed increasingly today because of successful cancer screening. We previously described the diagnostic category called atypical small acinar proliferation (ASAP), suspicious for but not diagnostic of malignancy, present in about 2.5% of routine prostatic needle biopsy specimens. OBJECTIVE: To establish the criteria enabling a distinction between ASAP and cancer. DESIGN: We prospectively evaluated clinical and histologic findings from all 319 patients consecutively diagnosed as having ASAP or minimal cancer by prostatic needle biopsy in a consultation service. Seventeen histopathologic features were assessed. RESULTS: Fifty-six patients (18%) had ASAP, and 100 (31%) had minimal cancer; the remaining 163 (51%) had benign diagnoses, high-grade prostatic intraepithelial neoplasia, or larger amounts of cancer. The mean age of patients with ASAP did not differ from that of patients with minimal cancer (64.2 years vs 63.3 years; P =.65). In 10 of 17 histopathologic findings, ASAP differed significantly from minimal cancer. Among architectural findings, ASAP foci averaged 0.4 vs 0.8 mm (P <.0001) and comprised a mean of 11 vs 17 acini (P <.0001). Infiltrative growth occurred in 75% of ASAP foci and 100% of minimal cancers (P <. 0001). Among cytologic findings, ASAP was significantly less likely than cancer to have mitotic figures (0% vs 10%, respectively; P <. 01) or prominent nucleoli in at least 10% of cells (55% vs 100%, respectively; P <.0001) and showed more frequent nuclear hyperchromasia (44% vs 9%, respectively; P <.0001) and less nuclear enlargement (P =.0002). Luminal blue mucin secretions were less common in ASAP than cancer (6% vs 33%, respectively; P <.0001), but eosinophilic granular secretions and crystalloids were about equally frequent. Concomitant high-grade prostatic intraepithelial neoplasia was present in 23% of ASAP cases and 57% of cancers (P <.0001). Moderate-to-severe atrophy confounded 59% of cases with ASAP and 35% of cancers (P =.003); both ASAP foci and cancer were associated with inflammation in about a quarter of cases. In each case with ASAP, we stratified our level of suspicion among 3 categories (favor benign, uncertain, and favor carcinoma). As suspicion increased so did the mean nuclear enlargement and percentage of cases with infiltrative growth and nuclear hyperchromasia (all P <.05). CONCLUSIONS: These criteria, which differ significantly between ASAP and minimal volume cancer, can help to separate patients for whom a second biopsy is recommended from candidates for prostatectomy or other therapy.

Adenocarcinoma↗
PubMed2000

Primary, localized vulvar B-cell lymphoma expressing CD44 variant 6 but not cadherins. A case report.

BACKGROUND: Primary extranodal lymphoma of the vulva is rare, with only 17 prior cases reported. Its immunohistochemical profile has not been characterized beyond B- or T-cell phenotype. CASE: A 64-year-old, white woman presented with a nontender enlargement of the right labium minus and labium majus. Bilateral vulvar punch biopsies revealed an infiltrate of neoplastic lymphocytes that filled the reticular dermis and extended down to the subcutaneous fat. Lymphoma cells were positive for CD20 and expressed CD43 in an aberrant manner. The tumor was examined for adhesion protein expression. There was expression of CD44 standard and variant 6 but not of E-, N- or P-cadherin. No systemic spread of this rare lymphoma was evident after one year. CONCLUSION: Adhesion protein expression in primary vulvar lymphoma may have prognostic implications.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

Cystic renal cell carcinoma is cured by resection: a study of 24 cases with long-term followup.

PURPOSE: The true incidence and biological behavior of cystic renal cell carcinoma are not known. To our knowledge we present the largest series of patients with cystic renal cell carcinoma with long-term followup. MATERIALS AND METHODS: We reviewed the Mayo Clinic surgical pathology files of renal cell cancer cases with a cystic component resected from 1969 to 1997, and arbitrarily chose 75% tumor involvement by cysts as a cutoff for inclusion in the study. RESULTS: We identified 24 cases of clear cell renal cell carcinoma with 75% or greater involvement by cysts comprising 0.79% of 3,047 renal cell cancer cases resected at our institution between 1969 and 1997. Mean patient age was 62.7 years (range 40 to 83). A total of 11 patients (46%) underwent radical nephrectomy, 4 (17%) simple nephrectomy, 3 (12%) partial nephrectomy and 6 (25%) tumor enucleation. Mean tumor involvement by cysts was 84% (range 75 to 95) and in 11 cases (46%) involvement was 90% or greater. Cancer stage was T1 in 20 patients (83%), T2 in 1 (4.4%) and T3a in 4 (12.5%). Cancers were diploid in all but 1 case. Mean followup was 77.6 months (range 8 to 428, median 51). A total of 22 patients (92%) had no evidence of cancer and 2 died of intercurrent disease. CONCLUSIONS: Our results indicate that cystic renal cell carcinoma is uncommon and usually cured by resection, regardless of size, stage or number of cysts. These patients may benefit from nephron sparing surgery, such as partial nephrectomy.

Adult↗
PubMed1999

Subepithelial pelvic hematoma of the kidney clinically mimicking cancer: report of six cases and review of the literature.

OBJECTIVES: Renal pelvic subepithelial hematoma is a rare but significant clinical mimic of neoplasm. Investigation and treatment of this diagnostic problem are uncertain. METHODS: We add 6 patients with this entity to the 15 previously published cases. All 6 were clinically suspected of having cancer, and 5 underwent nephrectomy. RESULTS: The most common clinical findings are gross hematuria (19 of 21 cases) and acute onset of flank pain (13 of 21 cases). Intravenous urogram usually reveals a filling defect at the ureteropelvic junction. Pathologic findings include massive subepithelial and peripelvic hemorrhage, hydronephrosis, cortical infarcts, and renomegaly. Two of our patients have previously undescribed clinical associations, including one who was 2 weeks postpartum and another with ureteropelvic junction obstruction. In addition, our patient with obstruction is the first with subepithelial hematoma to be treated successfully with pyeloplasty. CONCLUSIONS: Subepithelial pelvic hematoma may be effectively treated with pyeloplasty or partial nephrectomy if distinguished from cancer preoperatively. Awareness of this rare entity may allow preoperative identification, but this has not been possible to date.

Adult↗
PubMed1999

Does transurethral microwave thermotherapy have a different effect on prostate cancer than on benign or hyperplastic tissue?

OBJECTIVES: Transurethral microwave thermotherapy is useful for the treatment of benign prostatic hyperplasia, but its effect on cancer is not documented. We analyzed the pathologic changes occurring after microwave thermotherapy in whole mount radical prostatectomy specimens from patients with cancer. METHODS: Nine patients scheduled for radical prostatectomy for clinically localized prostate cancer were treated with transurethral microwave thermotherapy (Urologix Targis System). Patients ranged in age from 64 to 72 years (mean 68). Seven patients underwent prostatectomy 4 to 90 hours after thermotherapy, and 2 other patients underwent prostatectomy 12 months after thermotherapy. Whole mount totally embedded prostates were mapped for necrosis and cancer, and the volume of each was measured by the grid method. RESULTS: Pathologic stages were T2a (n = 4), T2b (n = 4), and T3b (n = 1). The prostates from patients who underwent radical prostatectomy within 4 to 90 hours of thermotherapy had a mean prostate weight of 47.4 g (range 19.5 to 70.3). Each consistently showed hemorrhagic necrosis and tissue devitalization without significant inflammation. Necrosis involved contiguous areas of benign epithelium, stroma, and cancer without skip areas. The mean volume of necrosis was 8.8 cc (range 1.4 to 17.8), and the mean percentage of the prostate involved by necrosis was 22% (range 3% to 39%). The necrosis was symmetric around the urethra in 6 of 7 cases. Urethral dilation was observed in 3 patients, and the mean maximum radial distance of necrotic tissue was 1.4 cm (range 0.6 to 1.8). Necrotic change was noted in 80% to 100% of the volume of cancer in 4 cases, 40% to 60% in 2 cases, and 5% in 1 case. The prostates from the 2 patients who underwent radical prostatectomy 12 months after thermotherapy had a mean weight of 88 g (55 and 121 g, respectively). Each showed periurethral fibrosis, nonspecific chronic inflammation, and squamous metaplasia of the urothelium. The mean volume of necrosis remaining was 0.2 cc. The mean percentage of the prostate involved by necrosis 1 year after thermotherapy was less than 1%. There was some reabsorption of dead tissue. The mean maximum radial distance of the necrotic tissue was 0.4 cm (0.2 and 0.7 cm, respectively). The prostatic urethra had viable and partially denuded urothelium in all cases. CONCLUSIONS: Microwave thermotherapy is clinically useful for ablation of benign prostate and cancer contiguous to the urethra, resulting in hemorrhagic necrosis with minimal damage to the urethra. There was no apparent differential morphologic sensitivity of benign prostatic tissue, hyperplastic tissue, or cancer to thermotherapy.

Aged↗
PubMed1999

Prostate biopsy interpretation. Current concepts, 1999.

Needle biopsy of the prostate has a pivotal role in the diagnosis of prostate cancer and the prediction of outcome. Strategies for sampling the prostate are being refined, which will increase the diagnostic yield. In combination with other clinical factors, the pathologic findings obtained from the biopsy specimen provide enhanced predictive accuracy for stage and individual outcome.

Atrophy↗
PubMed1999

Small cell carcinoma of urinary bladder is differentiated from urothelial carcinoma by chromogranin expression, absence of CD44 variant 6 expression, a unique pattern of cytokeratin expression, and more intense gamma-enolase expression.

AIMS: Small cell (neuroendocrine) carcinoma of the urinary bladder is clinically more aggressive than urothelial (transitional cell) carcinoma. We have investigated the immunohistochemical markers most useful in diagnosing small cell carcinoma in bladder. METHODS AND RESULTS: We evaluated the expression of chromogranin A, CD44 variant 6 (CD44v6), cytokeratin (CAM 5.2), gamma-enolase, synaptophysin, and CD45 in 46 small cell carcinomas of the bladder. Small cell and urothelial carcinoma were mixed in 21 (46%) cases. The two immunohistochemical markers with best ability to discriminate between small cell and urothelial carcinoma were chromogranin A and CD44v6. Chromogranin A had 97% specificity for small cell carcinoma, staining 65% of cases with 2+/3+ mean intensity; only one case (5%) of urothelial carcinoma was weakly (1+/3+) positive. CD44v6 was 80% specific for urothelial carcinoma, with immunoreactivity in 60% of cases, compared with 7% of small cell carcinoma cases. In cases positive for CD44v6, the mean percentage of reactive urothelial carcinoma cells was 75% (range 10-100%), greater than the 12% of cells in three cases of small cell carcinoma (P = 0.31); further, the pattern of immunoreactivity was membranous vs. focal cytoplasmic, respectively. All small cell carcinomas stained with one of the three neuroendocrine markers tested; 76% of cases were reactive for synaptophysin and 93% for gamma-enolase, with specificities of 86% and 73% in comparison to urothelial carcinoma. gamma-enolase staining of small cell carcinoma was more intense (P = 0.01) than for urothelial carcinoma. Cytokeratin CAM 5.2 stained a mean 47% of cells in small cell carcinoma, always in a punctate perinuclear pattern, and 75% in urothelial carcinoma, in a membranous pattern. CONCLUSIONS: CD44v6, chromogranin A, and possibly gamma-enolase and cytokeratin (CAM 5.2) help differentiate small cell carcinoma from urothelial carcinoma.

Adult↗
PubMed1999

Prostate biopsy 1999: strategies and significance of pathological findings.

Needle biopsy of the prostate plays a pivotal role in the diagnosis of prostate cancer and prediction of outcome. Strategies for sampling the prostate are being refined, which is increasing the diagnostic yield. In combination with other clinical factors, the pathological findings obtained from the biopsy specimen will provide enhanced predictive accuracy for stage and individual outcome.

Biopsy, Needle↗
PubMed1999

Steam heat with an EDTA buffer and protease digestion optimizes immunohistochemical expression of basal cell-specific antikeratin 34betaE12 to discriminate cancer in prostatic epithelium.

In select cases of prostatic carcinoma, antikeratin 34betaE12 immunohistochemical analysis is diagnostically useful for specific labeling of basal cells. This antibody, however, is prone to variability in staining, and the optimal conditions were not, to our knowledge, previously defined. We combined steam heat with EDTA buffer (steam-EDTA) and protease digestion (steam-EDTA + protease) to optimize epitope retrieval of antikeratin 34betaE12 in 42 cases of prostatic cancer. Results were judged by the percentage of cells staining and by staining intensity. In benign epithelium, steam-EDTA + protease significantly increased the percentage of immunoreactive cells (from 74 to 93%) and the intensity of staining (from 2.1 to 3.0 on a scale of 0-3+) by comparison with protease alone (all P<.001). In high-grade prostatic intraepithelial neoplasia, the percentage of cells staining increased from 55 to 73% and intensity increased from 1.7 to 2.8 (both P<.001). Steam-EDTA + protease also minimized variability in results between cases, with essentially no background stromal staining. Cancer was negative in all of our cases by both methods. We conclude that steam-EDTA + protease significantly enhances basal cell immunoreactivity compared with protease treatment alone in noncancerous prostatic epithelium. This helps to prevent misinterpretation of histologic mimics of cancer, such as atrophic acini and high-grade prostatic intraepithelial neoplasia, that result from false-negative staining.

Antibodies, Monoclonal↗
PubMed1998

Predictors of survival for prostate carcinoma patients treated with salvage radical prostatectomy after radiation therapy.

BACKGROUND: Salvage radical prostatectomy is a treatment option for patients with recurrent cancer following radiation therapy. This study was conducted to identify predictors of survival for patients treated with salvage radical prostatectomy. METHODS: The authors studied 86 prostate carcinoma patients who underwent salvage radical prostatectomy for locally persistent or recurrent prostate carcinoma at Mayo Clinic between 1967 and 1996. The mean interval from radiation therapy to biopsy-proven recurrence was 3.7 years (range, 6 months to 17 years). Patient age at surgery ranged from 51 to 78 years (median, 66 years). The mean follow-up after surgery was 5.8 years (range, 1.0-15.2 years). Cox proportional hazards models were used to identify clinical and pathologic factors associated with distant metastasis free survival and cancer specific survival. RESULTS: Actuarial distant metastasis free survival, cancer specific survival, and overall survival were 83%, 91%, and 85% at 5 years and 69%, 64%, and 54% at 10 years, respectively. In multivariate analysis, radical prostatectomy Gleason score and DNA ploidy were independent predictors of distant metastasis free survival and cancer specific survival. CONCLUSIONS: Postirradiation Gleason score and DNA ploidy were highly predictive of the clinical outcomes of patients treated by salvage radical prostatectomy after radiation therapy.

Aged↗