Deloar Hossain

Adenoid cystic/basal cell carcinoma of the prostate: clinicopathologic findings in 19 cases.

Adenoid cystic/basal cell carcinoma (ACBCC) of the prostate has been considered to have indolent biologic potential. However, outcome data are scant, with only one documented metastasis and death. We describe clinicopathologic features of ACBCC in 19 patients and document outcome in 15. Patients ranged in age from 43 to 83 years. All but one presented with urinary obstruction. ACBCC was diagnosed by transurethral resection in 15 cases, by needle biopsy in 3 cases, and unexpected in 1 case. Four patients had concurrent acinar adenocarcinoma. Histologically, cribriform or adenoid cystic patterns predominated in 12 cases and basal cell carcinoma pattern in 7. Five cases had prominent perineural invasion. ACBCC was immunoreactive for p63 and cytokeratins 7 and 34&bgr;E12 but not cytokeratin 20. After diagnosis, 5 patients underwent radical prostatectomy, 2 underwent pelvic exenteration, and the rest had no treatment. ACBCC showed extraprostatic extension in 5 cases and involved the bladder margin in 3. Metastases developed in 4 (21%) patients: liver (2), lung (2), bowel (1), and corpus cavernosum (1). In 15 cases with follow-up (0.3–11.8 years), two patients died of cancer (at 1.5 and 3 years after diagnosis), 3 remain alive with cancer, and 10 have no evidence of cancer. Thus, ACBCC of the prostate is a potentially aggressive neoplasm requiring ablative therapy.

Preoperative prediction of unifocal, unilateral, margin-negative, and small volume prostate cancer.

OBJECTIVES Contemporary prostate carcinoma is frequently of small volume and early stage. Subtotal gland ablation by minimally invasive therapies such as cryotherapy demands preoperative prediction of unifocal, unilateral, margin-negative, and small volume (less than 0.5 mL) cancer. METHODS We examined matched biopsy and prostatectomy and clinical data from 393 patients at two institutions who underwent surgery in 2000 through 2003. Radical prostatectomy specimens were uniformly sectioned at 5-mm intervals and completely embedded. Numerous clinical and biopsy variables were correlated by regression analysis with unifocal, unilateral, margin-negative, and 0.5 mL or less volume cancer in the prostatectomy specimen. Odds ratios (OR) were determined. RESULTS At prostatectomy, 92 (23%) had unifocal cancer, 90 (23%) had unilateral cancer, 348 (89%) had organ-confined cancer, and 106 (31%) had small volume cancer. Unilateral cancer occurred in 71% to 76% of cases of unilateral cancer in the biopsy (OR, 4.30; if 9 or more cores were sampled, OR rose to 6.83), and was predicted by unifocality in the biopsy (OR, 2.63). Unifocal cancer was predicted by unilateral (OR, 2.66) but not unifocal, cancer present in the biopsy. Negative surgical margins were predicted by unilateral (OR, 2.53; positive predictive value, 82%) cancer in the biopsy and by serum prostate specific antigen (OR, 5.33). Small volume cancer was predicted by unilateral (OR, 5.50) and unifocal (OR, 7.98) cancer in the biopsy; Gleason score greater than 7 predicted a non-small volume cancer (OR, 7.52). CONCLUSIONS Unilateral or unifocal cancer on biopsy are among the strongest predictors of unilateral, unifocal, and small volume prostate cancer in contemporary practice.

Prostatic stromal hyperplasia with atypia: follow-up study of 18 cases.

CONTEXT Prostatic stromal hyperplasia with atypia is a rare lesion that can be mistaken for sarcoma because of the presence of atypical, bizarre, degenerative myocyte nuclei. OBJECTIVE To determine the diagnostic criteria and clinical significance of prostatic stromal hyperplasia with atypia. DESIGN Eighteen cases of prostatic stromal hyperplasia with atypia were reviewed from the consultation file of one of the authors (D.G.B.). RESULTS Prostatic stromal hyperplasia with atypia consists of 1 or more ill-defined, uncircumscribed, hyperplastic stromal nodules, with variable numbers of atypical, bizarre giant cells, with vacuolated nuclei, smudged chromatin, and frequent multinucleation infiltrating around benign acini. There was a hypocellular, loose, myxoid stromal matrix, with ectatic hyalinized vessels and mild to moderate chronic inflammation. Stromal cells displayed intense immunoreactivity for androgen receptors and vimentin, but moderate reactivity for desmin and actin. There were 3 local recurrences, with a mean follow-up of 6.3 years (range, 0.5-14 years), but none developed evidence of sarcomatous transformation or malignancy. CONCLUSIONS Prostatic stromal hyperplasia with atypia is a rare, benign lesion, composed of degenerative myocytes with atypia that is histologically and clinically reminiscent of benign counterparts in the myometrium, breast, vulva, vagina, and elsewhere. Recognition of this distinctive entity should allow separation from phyllodes tumor and sarcoma of the prostate. The phrase stromal tumor of uncertain malignant potential is inappropriate for this benign tumor, and its use is discouraged.

Differentiation of melanoma and benign nevi by fluorescence in-situ hybridization.

Malignant melanoma is sometimes difficult to distinguish from benign nevus, and ancillary confirmatory studies would be of value in selected cases. To accurately differentiate melanoma from benign nevus, we investigated the utility of chromosomal anomalies in skin biopsy specimens using multitargeted fluorescence in-situ hybridization (FISH). Skin biopsy specimens were retrospectively collected from 63 patients diagnosed with benign compound nevus (n=32) or malignant melanoma (n=31); each diagnosis was independently confirmed before study by a second dermatopathologist. Unstained tissue sections were hybridized for 30 min using fluorescence-labeled oligo-DNA probes for chromosomes 6, 7, 11, and 20. Fluorescent signals for each chromosome were enumerated in 30 cells per case. Numeric chromosomal anomalies were found in 0% (0 of 32) of normal epidermis, 6% (two of 32) of compound nevi, and 94% (29 of 31) of melanomas (nevus vs. melanoma, P<0.0001). The mean number of cells with chromosomal changes was 23 in melanoma specimens, significantly higher than that in compound nevi (P<0.0001). The most frequent chromosomal anomaly in melanoma was gain of chromosome 11, followed consecutively by gains of chromosomes 7, 20, and 6. Chromosomal anomalies detected by FISH had an overall sensitivity of 94% and specificity of 94% in the separation of nevus and melanoma. With the use of oligo-DNA probes, multitargeted FISH directed against chromosomes 6, 7, 11, and 20 is highly sensitive and specific for separation of nevus and melanoma. Unlike other traditional FISH probes, oligo-DNA probes required shorter hybridization time, allowing faster diagnostic evaluation.

Improved filter method for urine sediment detection of urothelial carcinoma by fluorescence in situ hybridization.

CONTEXT Fluorescence in situ hybridization (FISH) of voided urine sediment is a sensitive and specific test for the detection of urothelial carcinoma. The time required for slide preparation using the conventional cytospin method is lengthy. OBJECTIVE To present an alternative to the conventional cytospin method. DESIGN We compared the results of an improved filter monolayer method with published results of the conventional cytospin method. A total of 624 patients with cytology and FISH analyses were followed with cystoscopy and/or bladder biopsy. Fluorescence in situ hybridization analysis was performed on 624 cases using fluorescence-labeled probes to the pericentromeric regions of chromosomes 3, 7, and 17 and band 9p21; cytology was also performed in all cases. RESULTS A total of 217 (34.7%) of 624 patients had follow-up bladder biopsies, and 170 of these (78.3%) had urothelial carcinoma. The sensitivity for cancer detection was higher for FISH than for urine cytology (92.9% [158/ 170] for FISH vs 72.9% [124/170] for urine cytology, P = <5%). The specificity was equivalent for FISH and urine cytology (97.5% [443/454] for FISH vs 92.2% [419/454] for cytology). The sensitivity for FISH was better (92.9% vs 81%), and there was no significant difference in specificity (97.5% vs 96%) between the filter method and the conventional cytospin method. Unlike the conventional cytospin method, the filter method did not require multiple centrifugation and decantation steps or investment in dedicated equipment. CONCLUSIONS The improved filter method was faster, easier, and less expensive than published results with the conventional cytospin method with better sensitivity and equivalent specificity.

Significance of the TMPRSS2:ERG gene fusion in prostate cancer.

Until recently, gene rearrangements, e.g. the Philadelphia chromosome, were thought to be most prevalent in haematological cancers, such as leukaemia. However, in 2005, most prostate cancers (up to 70%) were found to have fusion of the androgen-responsive genes transmembrane protease, serine 2 (TMPRSS2) and oestrogen-regulated gene (ERG), both on chromosome 21. Soon thereafter, other members of erythroblast transformation-specific (ETS) variant gene (ETV) family were found to have gene fusions, although at much lower frequencies, including ETV1 (chromosome 7), ETV4 (chromosome 17), ETV5 (chromosome 3), and ETS domain-containing protein gene (ELK4, chromosome 1) [1].

Precursor of prostate-specific antigen expression in prostatic intraepithelial neoplasia and adenocarcinoma: a study of 90 cases.

To assess the expression of the precursor of prostate‐specific antigen (pro‐PSA), a distinct molecular form of serum‐free PSA that includes native and truncated forms, in benign epithelium, high‐grade prostatic intraepithelial neoplasia (PIN) and prostatic adenocarcinoma.

Prostatic leiomyoma with atypia: follow-up study of 10 cases

We studied the clinical and histologic features of 10 cases of prostatic leiomyoma with atypical bizarre nuclei. Immunohistochemical studies were undertaken in 6 cases. Patient follow-up was obtained in all cases. Patients ranged in age from 50 to 82 years (mean, 65 years) and presented with urinary obstructive symptoms in 7 cases, abnormal digital rectal examination in 3 cases. The histologic findings consisted of a solid circumscribed expansile stromal nodule with abundant smooth muscle and variable numbers of atypical bizarre giant cells. The cells of the tumor displayed intense immunoreactivity for desmin, actin, and androgen receptor and weak to moderate reactivity for vimentin. Four local recurrences were seen, with a follow-up for 3 to 16 years (mean, 7.4 years), but no evidence of sarcomatous transformation occurred. Despite worrisome histologic appearance, a benign clinical behavior was seen in all cases.

Urinary β2-Microglobulin Is a Good Indicator of Proximal Tubule Injury: A Correlative Study with Renal Biopsies

Objective. After filtration through glomeruli, β2-microglobulin is reabsorbed in proximal tubules. Increased urinary β2-microglobulin indicates proximal tubule injury and measurement of β2-microglobulin in urine is useful to determine the source of renal injury. Kidney injury molecule-1 (KIM-1) has been characterized as a selective proximal tubule injury marker. This study was designed to evaluate the correlation of urinary β2-microglobulin concentration and KIM-1 expression as evidence of proximal tubule injury. Methods. Between 2009 and 2012, 46 patients with urine β2-microglobulin (RenalVysion) had follow-up kidney biopsy. Diagnoses included glomerular and tubule-interstitial disease. Immunohistochemical staining for KIM-1 was performed and the intensity was graded from 0 to 3+. Linear regression analysis was applied to correlate the values of urinary β2-microglobulin and KIM-1 staining scores. P < 0.05 was considered statistically significant. Results. Thirty patients had elevated urinary β2-microglobulin. KIM-1 staining was positive in 35 kidney biopsies. There was a significant correlation between urinary β2-microglobulin and KIM-1 staining (P < 0.05). Sensitivity was 86.6%, specificity was 43.7%, positive predictive value was 74.2%, and negative predictive value was 63.6%. Conclusion. Increased urinary β2-microglobulin is significantly correlated with KIM-1 staining in injured proximal tubules. Measurement of urine β2-microglobulin is a sensitive assay for proximal tubule injury.

Immunohistochemical Biomarkers of Prostatic Carcinoma

In recent years, advances in our understanding of the molecular biology of prostate cancer have spawned optimism that new biomarkers will allow greater sensitivity and specificity in diagnosis as well as more accurate prediction of outcome after treatment for the individual patient. For at-risk patients with negative biopsy, multiple new markers are available, including mitochondrial DNA deletion testing (tissue), PCA3 (urine), and sarcosine (tissue or blood). For patients with diagnostically challenging prostate biopsies, multiple stain combinations (multiplex immunohistochemistry) such as quadruple staining with racemase, high-molecular-weight cytokeratin, p63, and c-myc are commonly used to confirm the diagnosis of prostate cancer; the recent addition of c-myc to create a quadruple stain provides additional diagnostic support for cancer, recognizing that there may be heterogeneity or complete lack of staining for some of the other markers. These stain combinations must, of necessity, be used together on 1 slide owing to common loss of the focus of concern on deeper sections. TMPRSS2:ERG is a useful diagnostic adjunct for select cases, with the recent introduction of antibody staining. Prostate-specific antigen, prostatic acid phosphatase, and prostate-specific membrane antigen are useful for confirming prostatic origin of cancers, as well as for predicting outcomes for select patient group. Other biomarkers are being actively investigated as companion diagnostics to predict response to treatment. This report describes the current state of immunohistochemical stains for the diagnosis of prostatic intraepithelial neoplasia, atypical small acinar proliferation, and prostate cancer.