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Biomedical subjects

Anil V Parwani

Publications and source records attributed to Anil V Parwani.

At least 19 recordsLinked to original sources

Orthotopic expression of human 15-lipoxygenase (LO)-1 in the dorsolateral prostate of normal wild-type C57BL/6 mouse causes PIN-like lesions.

The lipid-peroxidating enzyme, 15-lipoxygenase (LO)-1 and its metabolite, 13-S-hydroxyoctadecadienoic acid (13-S-HODE), likely contribute to prostate tumorigenesis. Thus, this study evaluated adenovirus-mediated overexpression of 15-LO-1 on normal mouse prostate. Adenovirus expressing either human 15-LO-1 tagged with green fluorescent protein (GFP) or GFP alone was orthotopically injected into the dorsolateral prostates of C57BL/6 mice, three times over the course of 60 days. On day 90, pathological changes in prostate tissue were assessed by hematoxylin and eosin (H&E) staining. Expression of the proliferation marker Ki-67 was evaluated by immunohistochemistry and expression of angiogenesis markers were analyzed by an antibody array. Based on the latter study, immunoprecipitation analysis was used to measure the effect of 13-S-HODE, with or without conditioned media, on fibroblast growth factor-a and b (FGF-a and FGF-b) expression in human PrEC (normal prostate epithelial), PrSMC (normal prostate smooth muscle) and PrSC (normal prostate stromal) lines. Expression of viral 15-LO-1-GFP, but not GFP alone, resulted in the development of a prostate intraepithelial neoplasia (PIN)-like phenotype with increased expression of Ki-67. Aberrant 15-LO-1 expression also induced the angiogenic markers FGF-a and FGF-b. Human PrEC, PrSMC and PrSC lines demonstrated an increase in FGF-b expression upon stimulation with 13-S-HODE, which was further increased by the addition of conditioned media from the epithelial or smooth muscle cells. Using adenoviral mediated 15-LO-1 gene delivery, this study suggests that aberrant 15-LO-1 overexpression in normal prostate can trigger events leading to prostate epithelial and stromal cell proliferation. Thus, our findings demonstrate the effectiveness of this viral system for 15-LO-1 expression studies in tissues.

Adenoviridae↗

An informatics model for tissue banks--lessons learned from the Cooperative Prostate Cancer Tissue Resource.

BACKGROUND: Advances in molecular biology and growing requirements from biomarker validation studies have generated a need for tissue banks to provide quality-controlled tissue samples with standardized clinical annotation. The NCI Cooperative Prostate Cancer Tissue Resource (CPCTR) is a distributed tissue bank that comprises four academic centers and provides thousands of clinically annotated prostate cancer specimens to researchers. Here we describe the CPCTR information management system architecture, common data element (CDE) development, query interfaces, data curation, and quality control. METHODS: Data managers review the medical records to collect and continuously update information for the 145 clinical, pathological and inventorial CDEs that the Resource maintains for each case. An Access-based data entry tool provides de-identification and a standard communication mechanism between each group and a central CPCTR database. Standardized automated quality control audits have been implemented. Centrally, an Oracle database has web interfaces allowing multiple user-types, including the general public, to mine de-identified information from all of the sites with three levels of specificity and granularity as well as to request tissues through a formal letter of intent. RESULTS: Since July 2003, CPCTR has offered over 6,000 cases (38,000 blocks) of highly characterized prostate cancer biospecimens, including several tissue microarrays (TMA). The Resource developed a website with interfaces for the general public as well as researchers and internal members. These user groups have utilized the web-tools for public query of summary data on the cases that were available, to prepare requests, and to receive tissues. As of December 2005, the Resource received over 130 tissue requests, of which 45 have been reviewed, approved and filled. Additionally, the Resource implemented the TMA Data Exchange Specification in its TMA program and created a computer program for calculating PSA recurrence. CONCLUSION: Building a biorepository infrastructure that meets today's research needs involves time and input of many individuals from diverse disciplines. The CPCTR can provide large volumes of carefully annotated prostate tissue for research initiatives such as Specialized Programs of Research Excellence (SPOREs) and for biomarker validation studies and its experience can help development of collaborative, large scale, virtual tissue banks in other organ systems.

Databases as Topic↗

Primary histologic diagnosis using automated whole slide imaging: a validation study.

BACKGROUND: Only prototypes 5 years ago, high-speed, automated whole slide imaging (WSI) systems (also called digital slide systems, virtual microscopes or wide field imagers) are becoming increasingly capable and robust. Modern devices can capture a slide in 5 minutes at spatial sampling periods of less than 0.5 micron/pixel. The capacity to rapidly digitize large numbers of slides should eventually have a profound, positive impact on pathology. It is important, however, that pathologists validate these systems during development, not only to identify their limitations but to guide their evolution. METHODS: Three pathologists fully signed out 25 cases representing 31 parts. The laboratory information system was used to simulate real-world sign-out conditions including entering a full diagnostic field and comment (when appropriate) and ordering special stains and recuts. For each case, discrepancies between diagnoses were documented by committee and a "consensus" report was formed and then compared with the microscope-based, sign-out report from the clinical archive. RESULTS: In 17 of 25 cases there were no discrepancies between the individual study pathologist reports. In 8 of the remaining cases, there were 12 discrepancies, including 3 in which image quality could be at least partially implicated. When the WSI consensus diagnoses were compared with the original sign-out diagnoses, no significant discrepancies were found. Full text of the pathologist reports, the WSI consensus diagnoses, and the original sign-out diagnoses are available as an attachment to this publication. CONCLUSION: The results indicated that the image information contained in current whole slide images is sufficient for pathologists to make reliable diagnostic decisions and compose complex diagnostic reports. This is a very positive result; however, this does not mean that WSI is as good as a microscope. Virtually every slide had focal areas in which image quality (focus and dynamic range) was less than perfect. In some cases, there was evidence of over-compression and regions made "soft" by less than perfect focus. We expect systems will continue to get better, image quality and speed will continue to improve, but that further validation studies will be needed to guide development of this promising technology.

Journal Article↗

Urothelial carcinoma with rhabdoid features: report of 6 cases.

Extrarenal rhabdoid tumors have been described in a variety of primary sites with only rare case reports of urothelial carcinomas with rhabdoid features in the literature. In this report, we describe the clinicopathologic characteristics, including clinical follow-up on 6 cases of urothelial carcinoma with prominent rhabdoid features. Four cases were retrieved from the consultation files of one of the authors and 2 were retrieved from the surgical pathology files at our institution. The patients were all men, with ages ranging from 53 to 86 years (mean, 66.5 years). Patients initially presented with hematuria or obstructive symptoms. The sites included bladder (n = 4) and renal pelvis (n = 2). All cases had a prominent rhabdoid component (mean, 60%), ranging from 40% to 80%. In addition to the rhabdoid component, multiple coexistent histological components were seen, including in situ urothelial carcinoma (carcinoma in situ) and high-grade papillary urothelial carcinoma (n = 2), poorly differentiated carcinoma with small-cell features (n = 1), sarcomatoid (n = 2), and a myxoid component (n = 2). All cases in this series had focal or diffuse positive staining with one or more cytokeratin markers (epithelial membrane antigen, CAM 5.2, AE1/AE3). Of the 6 patients, 4 were treated initially with surgery (radical cystoprostatectomy, n = 2; radical nephrectomy, n = 2). Of 6 patients, 2 died within 1 month, whereas a third patient died within 4 months. The remaining 3 patients were alive at 3, 3, and 9 months after diagnosis. The histological and immunohistochemical findings in this study serve to broaden the morphological spectrum of urothelial carcinomas with prominent rhabdoid features and add further evidence as to their poor prognosis.

Aged↗

Use of whole slide imaging in surgical pathology quality assurance: design and pilot validation studies.

By imaging large numbers of slides automatically at high resolution, modem automated whole slide imaging (WSI) systems have the potential to become useful tools in pathology practice. This article describes a pilot validation study for use of automated high-speed WSI systems for surgical pathology quality assurance (QA). This was a retrospective comparative study in which 24 full genitourinary cases (including 47 surgical parts and 391 slides) were independently reviewed with traditional microscopy and whole slide digital images. Approximately half the cases had neoplasia in the diagnostic line. At the end of the study, diagnostic discrepancies were evaluated by a pathology consensus committee. The study pathologists felt that the traditional and WSI methods were comparable for case review. They reported no difference in perceived case complexity or diagnostic confidence between the methods. There were 4 clinically insignificant discrepancies with the signed-out cases: 2 from glass slide and 2 with WSI review. Of the 2 discrepancies reported by the WSI method, the committee agreed with the reviewer once and the original report once. At the end of the study, the participants agreed that automated WSI is a viable potential modality for surgical pathology QA, especially in multifacility health systems that would like to establish interfacility QA. The participants felt that major issues limiting the implementation of WSI-based QA did not involve image acquisition or quality but rather image management issues such as the pathologist's interface, the hospital's network, and integration with the laboratory information system.

Humans↗

Polyoma virus-associated cellular changes in the urine and bladder biopsy samples: a cytohistologic correlation.

Polyoma (BK) virus-type cellular changes are occasionally reported in urine specimens, yet rarely detected in histologic sections of bladder biopsies. A total of 762 predominantly voided urine specimens with a cytologic diagnosis of polyoma virus-type change were retrieved from the cytopathology files of the Johns Hopkins Hospital over a 15-year period (1988-2003). Biopsies were available for 33 cases (29 patients) following or preceding the urinary cytology (mean interval, 210 days). The biopsies originated primarily from bladder (n=31) with one biopsy each from renal pelvis and urethra. Representative paraffin blocks were chosen from each case for immunoperoxidase staining with SV40 large T antigen. There were 22 males and 7 females with an age range of 34 to 79 years (mean, 64.7 years). The histologic diagnoses of the 33 tissue biopsies were: benign urothelium (n=9), urothelial carcinoma (n=21) and 1 case each of dysplasia, small cell carcinoma, and chronic lymphocytic leukemia involving lamina propria of the bladder. Only 3 of 33 biopsies on hematoxylin-stained sections showed morphologic changes of polyoma virus, which lacked sufficient tissue to perform immunohistochemistry for SV40 large T antigen (LTag). Immunohistochemical staining for LTag was positive in 7 cases. Only 2 cases showed strong/diffuse and moderate/focal staining for LTag with both representing invasive high-grade urothelial carcinoma (where no inclusions were seen on hematoxylin and eosin-stained sections) and both demonstrating positive immunostaining for p53. One of these 2 cases was from an organ transplant recipient and the other from a patient with no known immunosuppression. Our data lead to the following conclusions: 1) cytology appears to be more sensitive than histology in detecting cells with polyoma virus; 2) cytohistologic discordance might be due to: a) polyoma (BK) virus infected cells are shed from the tissue and collected in the urine; b) polyoma virus changes may be focal and not sampled in directed tissue biopsies; c) polyoma virus changes may originate from sites in the genitourinary tract other than the bladder; d) the lack of a "gold standard" to confirm the cytologic diagnoses of polyoma virus; and e) the discordance in time between the biopsy and cytology specimens in the current retrospective study. 3) Because some cytologically benign cases of polyoma virus were associated with malignant biopsies, careful morphologic evaluation is required to avoid false-negative urinary cytology samples. This investigation further examined the immunohistochemical staining pattern for SV40 LTag and p53 in noninvasive low-grade papillary urothelial carcinoma using a tissue microarray constructed from bladder biopsies of 79 randomly selected patients. Weak LTag staining was present in occasional neoplastic urothelial cells of 2 patients. The staining was present in only one of four samples from each tumor (0.63%; 2 of 316 tumor spots), which further illustrates the patchy and focal presence of virion containing cells. p53 staining in these two spots was also patchy and confined to rare nuclei.

Adult↗

Pleomorphic giant cell adenocarcinoma of the prostate: report of 6 cases.

Pleomorphic tumors with giant cells have been described in a variety of primary sites. However, only a few cases have been described among prostatic carcinomas with only 1 on diagnostic biopsy material. Five cases were retrieved from the consultation files of one of the authors. One of the cases was retrieved from the surgical pathology files at our institute. Patient ranged in age from 59 to 76 years (mean=65.8 y). The diagnosis was made on needle biopsy (n=3), urethral biopsy (n=1), transurethral resection (n=1), or radical prostatectomy (n=1). In all cases, giant, bizarre, anaplastic cells were present. In 4 of the cases, marked pleomorphism occupied 5% of the specimen, with 20% and 70% bizarre giant cells in the other 2 cases. In one case, the bizarre cells had atypical mitotic figures, with other cases showing no mitoses in the markedly pleomorphic cells. In addition to the pleomorphic giant cell component, multiple coexistent histologic components were seen including Gleason score 9 conventional prostate cancer (n=6), small cell carcinoma (n=1), squamous carcinoma (n=1), and prominent ductal adenocarcinoma differentiation with intraductal spread (n=1). Immunohistochemically, 4 cases were for negative for prostate-specific antigen in the giant cells, 1 had 5% staining, and the other had 50% positivity in the giant cells. Staining for prostate-specific antigen in the conventional prostate carcinoma component was 1%, 5%, 20%, 50%, 100%, and 100%. The bizarre giant cells were strongly positive for cytokeratins AE1/AE3 and/or Cam 5.2 (n=3). Two cases had a history of conventional prostate cancer 4 years before the giant cell component, 1 treated with Lupron and the other with radiation. Follow-up after diagnosis of the giant cell component: Case 1: dead in 1 year of disease; Case 2: progressive metastases in 2 years; Case 3: alive at 1 year with disease; Case 4: large perineal recurrence after brachytherapy at 3 years; Case 5: radical prostatectomy with extraprostatic extension and seminal vesicle invasion; and Case 6: alive at 3 months, free of disease. Conventional prostate cancer, even when very high grade, typically consists of cells with relatively uniform nuclei. Our study expands the histology described in prostate cancer to include in very rare cases with prominent pleomorphism and bizarre giant cells. This giant cell component heralds a particularly aggressive clinical outcome.

Adenocarcinoma↗

Immunohistochemical staining of precursor forms of prostate-specific antigen (proPSA) in metastatic prostate cancer.

Precursors of prostate-specific antigen (proPSA) have been previously shown to be more concentrated in prostate cancer tissue. This study characterizes the immunohistochemical staining (IHS) of proPSA forms in metastatic prostate cancer compared with prostate specific antigen (PSA) and prostatic acid phosphatase (PAP). A tissue microarray, consisting of 74 cases of metastatic prostate carcinoma and control tissues, was used. IHS, using monoclonal antibodies against proPSA with a truncated proleader peptide containing 2 amino acids ([-2]pPSA), native ([-5/-7]pPSA), PSA, and PAP, was analyzed. The monoclonal antibodies were specific for both benign and malignant prostatic glandular tissue. IHS with [-5/-7]pPSA showed the least number of cases with negative staining (3%), and the most number of cases with moderate or strong staining (76%). In the 60 cases where all 4 stains could be evaluated, none of them were negative for proPSA and positive for PSA or PAP, and all 7 cases that were negative for both PSA and PAP showed IHS to proPSA. [-5/-7]pPSA (native proPSA) may be a better marker than PSA and PAP in characterizing metastatic prostate adenocarcinoma, with most of the cases showing positivity for the marker. Even cases that were negative for PSA and PAP, were reactive for proPSA. Such enhanced detection is particularly important in poorly differentiated carcinomas involving metastatic sites where prostate carcinoma is a consideration. A panel of markers, including proPSA, should be performed when metastatic prostate carcinoma is in the differential diagnosis.

Acid Phosphatase↗

Conditional expression of human 15-lipoxygenase-1 in mouse prostate induces prostatic intraepithelial neoplasia: the FLiMP mouse model.

The incidence and mortality of prostate cancer (PCa) vary greatly in different geographic regions, for which lifestyle factors, such as dietary fat intake, have been implicated. Human 15-lipoxygenase-1 (h15-LO-1), which metabolizes polyunsaturated fatty acids, is a highly regulated, tissue-specific, lipid-peroxidating enzyme that functions in physiological membrane remodeling and in the pathogenesis of atherosclerosis, inflammation, and carcinogenesis. We have shown that aberrant overexpression of 15-LO-1 occurs in human PCa, particularly high-grade PCa, and in high-grade prostatic intraepithelial neoplasia (HGPIN), and that the murine orthologue is increased in SV40-based genetically engineered mouse (GEM) models of PCa, such as LADY and TRansgenic Adenocarcinoma of Mouse Prostate. To further define the role of 15-LO-1 in prostate carcinogenesis, we established a novel GEM model with targeted overexpression of h15-LO-1 in the prostate [human fifteen lipoxygenase-1 in mouse prostate (FLiMP)]. We used a Cre- mediated and a loxP-mediated recombination strategy to target h15-LO-1 specifically to the prostate of C57BL/6 mice. Wild-type (wt), FLiMP+/-, and FLiMP+/+ mice aged 7 to 21, 24 to 28, and 35 weeks were characterized by histopathology, immunohistochemistry (IHC), and DNA/RNA and enzyme analyses. Compared to wt mice, h15-LO-1 enzyme activity was increased similarly in both homozygous FLiMP+/+ and hemizygous FLiMP+/- prostates. Dorsolateral and ventral prostates of FLiMP mice showed focal and progressive epithelial hyperplasia with nuclear atypia, indicative of the definition of mouse prostatic intraepithelial neoplasia (mPIN) according to the National Cancer Institute. These foci showed increased proliferation by Ki-67 IHC. No progression to invasive PCa was noted up to 35 weeks. By IHC, h15-LO-1 expression was limited to luminal epithelial cells, with increased expression in mPIN foci (similar to human HGPIN). In summary, targeted overexpression of h15-LO-1 (a gene overexpressed in human PCa and HGPIN) to mouse prostate is sufficient to promote epithelial proliferation and mPIN development. These results support 15-LO-1 as having a role in prostate tumor initiation and as an early target for dietary or other prevention strategies. The FLiMP mouse model should also be useful in crosses with other GEM models to further define the combinations of molecular alterations necessary for PCa progression.

Animals↗

Lipomatous hypertrophy of the interatrial septum: an overview.

Lipomatous hypertrophy of the interatrial septum is a rare, but increasingly recognized, anomalous developmental or neoplastic lesion of the heart. This entity was first described in 1964 at autopsy and is identified before death based on its distinctive characteristics on echocardiography, computed tomography, and magnetic resonance imaging. Although it is often asymptomatic, the mass has been associated with supraventricular arrhythmias and sudden death. In rare patients who experience intractable symptoms, surgical excision of the lesion may provide relief. Therefore, lipomatous hypertrophy of the interatrial septum is of interest to the pathologist when a cardiac mass is received for evaluation or at autopsy when a patient has experienced sudden death from an unknown cause.

Arrhythmias, Cardiac↗

Hepatocyte paraffin 1 immunoexpression in esophageal brush samples.

BACKGROUND: Intestinal metaplasia (IM) is often a component of Barrett esophagus (BE) and is characterized by a distinctive type of epithelium. Because IM has the potential to progress to dysplasia or adenocarcinoma, an accurate identification of its presence is important clinically. A cytopathologic diagnosis of IM on esophageal brushings by morphology alone can be difficult. The authors investigated the role of hepatocyte paraffin 1 (Heppar-1) immunostaining as a possible marker of IM in cytologic samples of BE. METHODS: Eleven samples each of BE with and without IM diagnosed on esophageal brushings were retrieved from the cytopathology files of The Johns Hopkins Hospital over an 8-year period (1993-2001). All 22 specimens were confirmed histologically on subsequent tissue biopsies. Slides initially were prepared by cytospin and stained with Papanicolaou stain. After destaining, the slides were immunostained with hepatocyte paraffin 1 (Heppar-1) antibody at 1:100 dilution employing conventional methodology. RESULTS: Among the samples of BE with IM, 9 of 11 samples (82%) were immunoreactive for Heppar-1, compared with 0 of 11 specimens of BE with only cardiac-type metaplasia. The immunoexpression was cytoplasmic and granular and was seen only focally in the glandular fragments. CONCLUSIONS: Heppar-1 was a moderately sensitive (82%) and highly specific (100%) immunomarker for IM in BE. It was easy to use in limited cytologic samples that originally were stained with Papanicolaou stain and is recommended for inclusion in morphologically difficult samples of BE with questionable IM. The immunostaining pattern predominantly was focal, necessitating a careful evaluation of positive reactions on cytologic samples.

Adenocarcinoma↗

Pineal gland lesions: a cytopathologic study of 20 specimens.

BACKGROUND: Pineal gland lesions are rare, with only a few cytologic descriptions occurring in the literature, according to the authors' knowledge. The current article describes the cytopathologic characteristics of 20 such lesions with discussion of differential diagnoses. METHODS: Cytologic material was obtained either by fine-needle aspiration biopsy (FNAB) under stearotactic radiologic guidance or by touch imprinting (TI) at the time of frozen sectioning. The 20 specimens include pineoblastoma (five specimens), pineocytoma (four specimens), astrocytoma (three specimens), germ cell tumor (three specimens), meningioma (one specimen), epidermoid cyst (three specimens), and pineal cyst (one specimen). Smears were stained with Diff-Quik and with Papanicolaou and hematoxylin and eosin stains. In selected specimens, immunoperoxidase (IPOX) stains were performed on cell block sections using synaptophysin, neuron-specific enolase, placental alkaline phosphatase, glial fibrillary acidic protein, leukocyte common antigen, cytokeratins, and human chorionic gonadotropin antibodies. RESULTS: Several cytomorphologic characteristics unique to each lesional category with occasional overlapping features were observed. The unique features included the following: small, hyperchromatic, round to oval cells with frequent rosetting (pineocytoma), with a few specimens in addition showing hypercellularity, crowding, mitoses, and necrosis (pineoblastoma); pleomorphic round cells in a fibrillary background (astrocytoma); large polygonal cells with prominent nucleoli and clear cytoplasm (germ cell tumor); spindled fibroblastic cells (meningioma); anucleate squames and mature squamous cells (epidermoid cyst); and small uniform polygonal cells (pineal cyst). When necessary, IPOX studies supported the morphologic diagnoses. CONCLUSIONS: FNAB and TI cytology were found to provide a rapid and reliable diagnosis of pineal lesions. This is particularly important when dealing with minute amounts of tissue material. Both techniques appeared to provide equally good cytomorphology on smears. IPOX studies played an important complementary role in difficult cases when performed on cell blocks.

Adolescent↗

Atypical teratoid/rhabdoid tumor of the brain: cytopathologic characteristics and differential diagnosis.

BACKGROUND: Atypical teratoid/rhabdoid tumor (AT/RT) is a highly aggressive neoplasm with a unique cytogenetic profile. Although the clinicopathologic and radiologic features of AT/RT have been described previously, to the authors' knowledge the cytomorphologic profile of this tumor has not been studied well. METHODS: Nine samples of AT/RT from 8 patients were analyzed from the pathology files of 2 large institutions in a 10-year period (1993-2002). Material consisted of slides made from scraping and smearing (SS) or squash preparation (SP) of the tissue cores (six slides), fine-needle aspiration (FNA) (two slides), and cerebrospinal fluid (one slide). Smears were stained with Diff-Quik, Papanicolaou, and hematoxylin and eosin stains. RESULTS: There were 4 males and 4 females who ranged in age from 1-16 years (mean age, 7.1 years). Cytomorphologic features consisted of hypercellularity (eight of eight tumors); predominantly large tissue fragments with tumor cells surrounding proliferating capillaries depicting a "papillary-like" appearance (five of eight tumors); large, round, "plasmacytoid" cells and characteristic "rhabdoid" cells (i.e., intermediate-sized cells with granular to fibrillary, brightly eosinophilic cytoplasm with or without globoid "inclusions"; large, eccentrically located, round-to-reniform nuclei with single prominent nucleoli; eight of eight tumors); small, round, primitive "neuronal-appearing" cells with a high nuclear to cytoplasmic ratio (five of eight patients); and bizarre, multinucleated giant cells (two of eight tumors). Also seen were numerous apoptotic bodies, mitoses, and significant necrosis (seven of eight tumors), and prominent dystrophic calcification (four of eight tumors). CONCLUSIONS: AT/RT is extremely rare. Cytologic examination by SS, SP, or FNA offers a useful alternative to frozen section during intraoperative consultation. Cytomorphologic features are unique and lead to an accurate diagnosis in the right clinicoradiologic context. The differential diagnosis includes medulloblastoma (in cerebellar tumors), primitive neuroectodermal tumor (in suprasellar tumors), choroid plexus carcinoma, and malignant glioma.

Adolescent↗

Cervical adenoid basal tumors comprised of adenoid basal epithelioma associated with various types of invasive carcinoma: clinicopathologic features, human papillomavirus DNA detection, and P16 expression.

Adenoid basal tumors are uncommon cervical lesions that some pathologists consider invasive carcinomas but others consider "epitheliomas" due to their low-grade histological appearance and rarely documented malignant behavior. We report the clinicopathologic features of 10 tumors comprised of both typical low-grade adenoid basal tumors (epitheliomas) intimately associated with invasive carcinomas having infiltrative growth, increased cytological atypia and mitotic activity, and various types of differentiation, including adenoid basal/squamous, pure squamous, adenoid cystic, and small cell neuroendocrine. Tumors were evaluated for the presence of human papillomavirus (HPV) DNA and immunohistochemical p16 expression. The patients in the study group ranged in age from 45 to 81 years (mean, 65 years). Most of the patients presented with abnormal cervicovaginal smears. The initial diagnosis was made on specimens obtained by cervical biopsy, laser electrocautery excision procedure (LEEP), or cone biopsy in 8 patients. Two 2 patients were incidentally diagnosed in hysterectomy specimens. All 10 patients had squamous intraepithelial lesions (9 high-grade, 1 low-grade). In all cases diagnosed in LEEP or cone biopsy specimens, the invasive carcinoma component was present in the excisional specimen and extended to the margins. Seven patients diagnosed on excisional or biopsy specimens who underwent hysterectomy had residual tumor in the cervix, ranging from microscopic foci to deeply invasive. No lymph node metastases were identified in 4 patients who were staged. Seven patients with follow-up were alive without evidence of disease after follow-up intervals of 8 to 84 months (mean, 45 months; median, 29 months). One patient with a component of small cell carcinoma died of other causes without evidence of disease at 18 months. HPV 16 DNA was detected in both the adenoid basal epithelioma and invasive carcinoma components in 9 tumors by in situ hybridization, and HPV 33 was detected by polymerase chain reaction in 1 tumor. All tumors expressed p16 diffusely. Adenoid basal tumors are high-risk HPV-related tumors that can be comprised of both a low-grade adenoid basal tumor, which can be designated as epithelioma, and invasive carcinomas of various types. The invasive component is usually evident in the excisional biopsy specimen, allowing for recognition of a tumor that needs further management.

Aged↗

Glomus tumor of renal pelvis: a case report and review of the literature.

Glomus tumors are uncommon benign perivascular neoplasms that have rarely been described outside of their usual peripheral soft tissue sites. We report a unique case of glomus tumor of the renal pelvis in a 53-year-old woman who presented with microscopic hematuria associated with obstruction of the ureteropelvic junction and marked hydronephrosis. At initial gross examination, the tumor mimicked a urothelial carcinoma.

Diagnosis, Differential↗

Small glandular proliferations on needle biopsies: most common benign mimickers of prostatic adenocarcinoma sent in for expert second opinion.

The current study aimed to determine the incidence of various benign mimickers of prostatic adenocarcinoma most commonly encountered in a busy consultation practice. All prostate needle biopsies from the consult service of one of the authors were prospectively evaluated over a 7-month period. Only cases with foci where the contributor questioned malignancy and which upon expert review the entire case was determined to be benign were included in this study. A total of 567 separate suspected atypical foci from 345 patients of a total of 4,046 patients (8.5%) received in consultation were identified. Of these, 281 foci (49.5%) had immunohistochemical (IHC) studies performed by the outside institution, which included high molecular weight cytokeratin (HMWCK) (n = 280), alpha-methylacyl-CoA racemase (AMACR) (P504s) (n = 45), and p63 (n = 34). The most common mimicker was partial atrophy (203 of 567; 35.8%). Technically adequate IHC for basal cells was performed in 117 cases of partial atrophy with patchy or patchy/negative staining seen in 102 of 117 (87%), with the remaining 13% of cases completely negative. A total of 15 of 19 (79%) cases of partial atrophy were positive with AMACR. Crowded benign glands, insufficiently crowded or numerous to warrant a diagnosis of adenosis, was the second most common mimicker (146 of 567; 25.7%). Crowded benign glands had patchy or patchy/negative IHC for basal cells in 66 of 81 (81%) cases with the remaining 19% of cases completely negative. A total of 7 of 11 (64%) cases of crowded glands were positive for AMACR. In the past, complete atrophy, adenosis, seminal vesicle, and granulomatous prostatitis were considered common mimickers of prostate cancer on prostatic needle biopsies. Our study shows that currently partial atrophy and crowded benign glands are the most common benign changes causing diagnostic difficulty and prompting consultation. Negative or patchy staining for basal cells and positive staining for AMACR may contribute to diagnostic difficulty in these entities.

Adenocarcinoma↗