Biomedical subjects

Stacey E Mills

Publications and source records attributed to Stacey E Mills.

At least 19 recordsLinked to original sources

PubMed2006

Case-matched comparison of contemporary radiation therapy to surgery in patients with locally advanced prostate cancer.

PURPOSE: Few studies critically compare current radiotherapy techniques to surgery for patients with locally advanced prostate cancer, despite an urgent need to determine which approach offers superior cancer control. Our objective was to compare rates of biochemical relapse-free survival (BFS) and surrogates of disease specific survival among men with high risk adenocarcinoma of the prostate as a function of treatment modality. METHODS AND MATERIALS: Retrospective data from 409 men with prostate-specific antigen (PSA) > or =10 or Gleason 7-10 or Stage > or =T2b cancer treated uniformly at one university between March 1988 and December 2000 were analyzed. Patients had undergone radical prostatectomy (RP), brachytherapy implant alone (BTM), or external beam radiotherapy with brachytherapy boost with short-term neoadjuvant and adjuvant androgen deprivation therapy (BTC). From the total study population a 1:1 matched-cohort analysis (208 patients matched via prostate-specific antigen, Gleason score) comparing RP with BTC was performed as well. RESULTS: Estimated 4-year BFS rates were superior for patients treated with BTC (BTC 72%, BTM 25%, RP 53%; p < 0.001). Matched analysis of BTC vs. RP confirmed these results (BTC 73%, BTM 55%; p = 0.010). Relative risk (RR) of biochemical relapse for BTM and BTC compared with RP were 2.92 (1.95-4.36) and 0.56 (0.36-0.87), (p < 0.001, p = 0.010). RR for BTC from the matched cohort analysis was 0.44 (0.26-0.74; p = 0.002). CONCLUSIONS: High-risk prostate cancer patients receiving multimodality radiation therapy (BTC) display apparently superior BFS compared with those receiving surgery (RP) or brachytherapy alone (BTM).

Aged↗

PubMed2006

Hyalinizing trabecular adenoma of the thyroid revisited: a histologic and immunohistochemical study of thyroid lesions with prominent trabecular architecture and sclerosis.

BACKGROUND: Since its description, hyalinizing trabecular adenoma (HTA) of the thyroid has been a controversial entity. Some have considered it a unique entity, some have considered it a variant of papillary carcinoma (PC), and still others have considered it a nonspecific pattern that may be seen with a variety of thyroid lesions. Complicating the matter, studies demonstrating metastases have shown entities that do not appear to be HTAs as originally described, and molecular studies showing changes of PC have used methods that are not specific. This study reviews our experience with thyroid lesions that showed at least some histologic features of HTA and presents the immunohistochemical findings for these lesions using antibodies employed for the diagnosis of PC. DESIGN: Our files were reviewed for all thyroid resection reports describing lesions with hyalinized or sclerotic stroma and a trabecular architecture within the diagnosis or diagnostic comment. All cases were reviewed and classified as either HTA or as different lesions based upon histologic features. Immunohistochemistry with antibodies to HBME1, CK19 and p63 was performed with all lesions and with a series of controls. RESULTS: Eighteen thyroid lesions with prominent sclerosis or hyalinization and trabecular architecture were identified. Only 4 of these were found to completely match the histologic and cytologic descriptions of HTA by HE review. The other cases showed histologic features more compatible with other diagnoses including cellular adenomatoid nodule (5), follicular adenoma (4), follicular variant of PC (FVPC) (3), and epithelial neoplasm with features of FVPC (2). All HTAs lacked immunoreactivity for HBME1, CK19 and p63. All cases deemed to be adenomatoid nodules, follicular adenomas and epithelial neoplasms showed no immunoreactivity for HBME1 and CK19 and, of these, only a single AN showed immunoreactivity for p63. Cases deemed to be FVPCs showed diffuse immunoreactivity for HBME1 and CK19 and 1 reacted with antibodies to p63. Of control PCs and other thyroid lesions, reactivity for HBME1, CK19, and p63 was observed in 8/8, 7/7, and 7/8 and 3/27, 7/27, and 7/27 cases, respectively. CONCLUSIONS: A sclerotic or hyalinized stroma with a trabecular growth pattern may be seen in a number of different thyroid lesions and, when seen, is usually a focal feature of a lesion other than HTA. Immunohistochemistry may be of assistance as cases of FVPC with prominent hyalinization and trabeculation will show immunoreactivity for HBME1 and CK19, whereas HTAs and other thyroid lesions with hyalinization and trabeculation will not.

Adenoma↗

PubMed2006

The mismatch repair protein status of colorectal small cell neuroendocrine carcinomas.

Small cell neuroendocrine carcinoma (SCNC) of the colorectum is a rare and highly aggressive malignancy. It can be associated with conventional-type adenocarcinoma, and an overlying adenoma can often be identified. A disproportionate number has been noted to arise in the right colon. Although some phenotypes (eg, mucinous adenocarcinoma) have been shown to be associated with deficient mismatch repair (MMR) and thus microsatellite instability (MSI), the MMR protein status of colorectal SCNCs has not been investigated. This study investigated the status of 3 MMR proteins, hMLH1, hMSH2, and hMSH6, in SCNCs of the colorectum. Fifteen SCNCs were identified on the basis of previous descriptions and the World Health Organization histologic criteria for the diagnosis of pulmonary small cell carcinoma and immunohistochemical evidence of epithelial and neuroendocrine differentiation. Patient age and sex and tumor size and location were recorded. Immunohistochemistry was performed with antibodies to pancytokeratin (cocktail), CD56, neuron specific enolase, synaptophysin, chromogranin, hMLH1, hMSH2, and hMSH6. Patients' ages ranged from 44 to 87 years (mean age = 73 y) and there were 9 men and 6 women. Tumors were located in the right colon (6), sigmoid colon (4), and rectum (3) (the locations of 2 cases were not recorded) and ranged in size from 0.4 to 15 cm in greatest dimension (mean = 6.6 cm). All tumors showed immunoreactivity with antibodies to pancytokeratin and with antibodies to at least 1 neuroendocrine antigen. MMR proteins were intact by immunohistochemistry in all but a single case that had neither an identifiable precursor lesion nor positive internal control (hMLH1 loss). Colorectal SCNCs are rare and are often right-sided. They are aggressive and tend to occur in older individuals. Most colorectal SCNCs have intact MMR proteins, suggesting that they develop secondary to chromosomal instability rather than MSI. Our single case showing potential MMR protein loss suggests that this phenotype may be independent of the developmental pathway (ie, chromosomal instability vs. MSI). This may explain the rare cases of SCNC that have been identified in patients with hereditary nonpolyposis colon cancer.

Adaptor Proteins, Signal Transducing↗

PubMed2006

Anorectal malignant melanoma: morphologic and immunohistochemical features.

We reviewed 17 cases of primary anorectal malignant melanoma. Morphologic features evaluated included junctional change, pigmentation, morphology, and mitotic rate. Immunohistochemical stains were performed for/with S-100 protein, HMB-45, MelanA, tyrosinase, vimentin, KIT, and pankeratin. Morphologic subtypes were as follows: epithelioid, 12 cases; spindle cell, 7 cases; lymphoma-like, 10 cases; and pleomorphic, 6 cases. Pigmentation was present in 9 cases. Junctional change was present in 6 cases. The mitotic rate was 3 or more per high-power field in 8 cases. S-100 protein was present in all cases, HMB-45 stained 16 of 17, MelanA was present in 14 of 15, tyrosinase in 12 of 14, vimentin in 13 of 14, and KIT in 12 of 16. Pankeratin was absent in all cases. The mean length of follow-up was 25.6 months (range, 8-96 months), and the average survival with disease was 32.3 months (range, 8-96). No morphologic or immunohistochemical features were predictive of survival. Anorectal malignant melanoma shows considerable morphologic variability. Immunohistochemical staining is similar to cutaneous melanomas. Expression of KIT was present frequently, including cases with spindle cell morphologic features, in which it may lead to confusion with gastrointestinal stromal tumors.

Aged↗

PubMed2005

Evidence-based principles and practices in pathology: selected problem areas.

Contrary to the intuitive impression of most pathologists, there are still many areas in laboratory medicine where evidence-based medicine (EBM) principles are not applied. These include aspects of both anatomic and clinical pathology. Some non-EBM practices are perpetuated by clinical "consumers" of laboratory services, because of inadequate education, habit, or over-reliance on empirical factors. Other faulty procedures are pathologist-driven, with similar underpinnings. This overview considers several exemplary problem areas representing non-EBM practices in the hospital laboratory. Such examples include ideas and techniques centering on metastatic malignancies, "targeted" oncological therapy, analysis of surgical margins in the excision of neoplasms, general laboratory testing and data utilization, evaluation of selected coagulation defects, administration of blood products, and analysis of hepatic iron-overload syndromes. The concepts illustrating departures from EBM are discussed for each of those topics.

Blood Coagulation↗

PubMed2005

KIT and RCC are useful in distinguishing chromophobe renal cell carcinoma from the granular variant of clear cell renal cell carcinoma.

The distinction between chromophobe renal cell carcinoma, the granular cell variant of clear cell renal cell carcinoma, and renal oncocytoma is a common diagnostic dilemma. The usefulness of KIT, CD10, RCC, and RON in the differential diagnosis of these renal epithelial tumors was investigated. KIT was 100% positive in chromophobe renal cell carcinoma (11 of 11) and renal oncocytoma (12 of 12). The KIT staining pattern was identical in both tumor types, with cytoplasmic membrane attenuation, and fine granular cytoplasmic staining. In contrast, KIT was absent in all granular cell variants of clear cell renal cell carcinoma (0 of 6). RCC was observed in more than 80% of the granular cell variant of clear cell renal cell carcinoma (5 of 6) but was negative in all chromophobe renal cell carcinomas (0 of 11) and renal oncocytomas (0 of 12). CD10 was expressed in 100% of the granular cell variant of clear cell renal cell carcinoma (6 of 6), 72% of chromophobe renal cell carcinomas (8 of 11), and 58% of renal oncocytomas (7 of 12). RON was 100% positive in the chromophobe renal cell carcinomas (11 of 11) and renal oncocytomas (12 of 12) but only 50% positive in the granular cell variant of clear cell renal cell carcinoma (3 of 6). Colloidal iron was diffusely and strongly positive in more than 80% of the chromophobe renal cell carcinomas (9 of 11), focally and weakly positive in 41% of the renal oncocytomas (5 of 12) but negative in all granular cell variant of clear cell renal cell carcinoma (0 of 6). The above results demonstrate that: 1) KIT is a very sensitive marker for both chromophobe renal cell carcinoma and renal oncocytoma; 2) immunohistochemistry using antibodies to KIT combined with RCC was sufficient to discriminate between chromophobe renal cell carcinoma and the granular cell variant of clear cell renal cell carcinoma; and 3) neither RON, nor KIT, nor a combination of this panel can be used to distinguish chromophobe renal cell carcinoma from renal oncocytoma. Colloidal iron staining aided in this distinction for the majority of the chromophobe renal cell carcinomas (more than 80% positive) and renal oncocytomas (close to 60% negative).

Adenocarcinoma, Clear Cell↗

PubMed2005

"Undifferentiated" small round cell tumors of the sinonasal tract: differential diagnosis update.

Sinonasal tract neoplasms composed of light microscopically seemingly "undifferentiated" small round cells often generate considerable diagnostic difficulty. Although the careful review of H&E-stained sections remains of critical and central importance in this evaluation, the recent improvements in the immunohistochemical diagnostic armamentarium and molecular diagnostic techniques applicable to paraffin-embedded tissue samples may add diagnostically valuable information. Accordingly, this review will discuss the differential diagnosis of undifferentiated small blue cell tumors of the sinonasal tract based on the light microscopic and clinical features and, as needed, the results of these ancillary studies. Tumors discussed include olfactory neuroblastoma, sinonasal undifferentiated carcinoma, small cell undifferentiated (neuroendocrine) carcinoma, undifferentiated (lymphoepithelioma-like) carcinoma, malignant melanoma, pituitary adenoma, Ewing sarcoma/peripheral neuroectodermal tumor, rhabdomyosarcoma, mesenchymal chondrosarcoma, small cell osteosarcoma, synovial sarcoma, extranodal natural killer/T-cell lymphoma, nasal type, and extramedullary plasmacytoma.

Carcinoma, Small Cell↗

PubMed2005

Squamous cell carcinoma variants of the upper aerodigestive tract.

Squamous cell carcinoma (SCC) is by far the most common malignancy of the upper aerodigestive tract. Most conventional-type SCCs do not present the surgical pathologist with diagnostic difficulty. Certain variants, however, can histologically mimic benign and other malignant diseases. In such cases, correct diagnosis is important for prognostic and therapeutic reasons. This article discusses the clinicopathologic features of the upper aerodigestive tract variants of SCC, including verrucous carcinoma, papillary squamous cell carcinoma, basaloid squamous cell carcinoma, spindle cell carcinoma, adenosquamous carcinoma, adenoid squamous cell carcinoma, and undifferentiated carcinoma. It also discusses the differential diagnoses that must be considered and the use of ancillary testing, especially immunohistochemical analysis, for determining the correct diagnosis.

Carcinoma, Adenosquamous↗

PubMed2005

Sporadic medullary carcinoma of the colon: a clinicopathologic comparison with nonhereditary poorly differentiated enteric-type adenocarcinoma and neuroendocrine colorectal carcinoma.

We studied 68 sporadic colorectal carcinomas (CRCs) with medullary features (MCRCs) and compared them with 35 poorly differentiated purely "enteric" CRCs (ECRCs) and 15 purely neuroendocrine carcinomas (NECs) of grades II and III, all in patients lacking a family history of CRC. Potential clinicopathologic differences between the study groups were assessed. MCRCs were significantly more common in the ascending colon than were ECRCs, but there was no significant dissimilarity to NECs. ECRCs occurred more often in the rectosigmoid than MCRCs or NECs. MCRCs arose in older patients, and a marked sex difference also was noted. Despite an infiltrative growth pattern, MCRC was less likely than ECRC to manifest with stage III or IV disease, but there was no stage-related difference from NECs. Although the histologic images of MCRCs were evocative of neuroendocrine differentiation, chromogranin positivity and synaptophysin reactivity in that group did not differ meaningfully from that of ECRCs but was dissimilar to the 100% labeling of NECs. p53 immunolabeling was similar in the 3 tumor groups. Follow-up data in the study cases showed that 5-year mortality was 40% (27/68) for MCRC, 59% (19/32) for ECRC, and 93% (14/15) for NEC. Medullary CRC seems to be a distinct clinicopathologic variant of CRC, which does not have a neuroendocrine lineage. The biologic behavior of MCRC was better than that of ECRC or NEC.

Adenocarcinoma↗

PubMed2004

Epstein-Barr virus plays no role in the tumorigenesis of small-cell carcinoma of the lung.

Epstein-Barr virus infection has been associated with lymphoepithelioma-like carcinoma of the lung in Asian patients. Recently, Epstein-Barr virus proteins or genomic DNAs were detected in pulmonary squamous-cell carcinoma, adenocarcinoma, and undifferentiated small-cell carcinoma in American patients. We studied 23 cases of small-cell carcinoma of the lung for evidence of Epstein-Barr virus infection by in situ hybridization, immunohistochemistry, and polymerase chain reaction methods. Of the 23 cases, 13 cases were primary small-cell carcinoma of the lung and 10 cases were metastatic small-cell carcinoma of the lung to the brain (one case), liver (two cases), and lymph nodes (seven cases). None of the 23 cases was positive for Epstein-Barr virus-encoded small nonpolyadenylated RNA (EBER)-1 by in situ hybridization. By immunohistochemistry, eight cases showed focal positivity for Epstein-Barr virus nuclear antigen-1. The positive immunostaining was focal and was observed in tumor cells, vascular endothelial cells, and lymphocytes, suggesting nonspecific staining. None of the 23 cases was positive for the transactivating immediate-early BZLF1 (ZEBRA) and latent membrane protein (LMP-1). Only one case was positive for the BamHI W region and LMP-1 gene by polymerase chain reaction assay. Some tumor cells in the BamHI W region positive case were also positive for Epstein-Barr virus nuclear antigen-1. Our study indicates that rare cases of American small-cell carcinoma of the lung may contain Epstein-Barr virus-infected cells, but it is unlikely that Epstein-Barr virus plays a role in the tumorigenesis of small-cell carcinoma of the lung.

Biomarkers, Tumor↗

PubMed2004

Most osteomalacia-associated mesenchymal tumors are a single histopathologic entity: an analysis of 32 cases and a comprehensive review of the literature.

Oncogenic osteomalacia (OO) is a rare paraneoplastic syndrome of osteomalacia due to phosphate wasting. The phosphaturic mesenchymal tumor (mixed connective tissue variant) (PMTMCT) is an extremely rare, distinctive tumor that is frequently associated with OO. Despite its association with OO, many PMTMCTs go unrecognized because they are erroneously diagnosed as other mesenchymal tumors. Expression of fibroblast growth factor-23 (FGF-23), a recently described protein putatively implicated in renal tubular phosphate loss, has been shown in a small number of mesenchymal tumors with known OO. The clinicopathological features of 32 mesenchymal tumors either with known OO (29) or with features suggestive of PMTMCT (3) were studied. Immunohistochemistry for cytokeratin, S-100, actin, desmin, CD34, and FGF-23 was performed. The patients (13 male, 19 female) ranged from 9 to 80 years in age (median 53 years). A long history of OO was common. The cases had been originally diagnosed as PMTMCT (15), hemangiopericytoma (HPC) (3), osteosarcoma (3), giant cell tumor (2), and other (9). The tumors occurred in a variety of soft tissue (21) and bone sites (11) and ranged from 1.7 to 14 cm. Twenty-four cases were classic PMTMCT with low cellularity, myxoid change, bland spindled cells, distinctive "grungy" calcified matrix, fat, HPC-like vessels, microcysts, hemorrhage, osteoclasts, and an incomplete rim of membranous ossification. Four of these benign-appearing PMTMCTs contained osteoid-like matrix. Three other PMTMCTs were hypercellular and cytologically atypical and were considered malignant. The 3 cases without known OO were histologically identical to the typical PMTMCT. Four cases did not resemble PMTMCT: 2 sinonasal HPC, 1 conventional HPC, and 1 sclerosing osteosarcoma. Three cases expressed actin; all other markers were negative. Expression of FGF-23 was seen in 17 of 21 cases by immunohistochemistry and in 2 of 2 cases by RT-PCR. Follow-up (25 cases, 6-348 months) indicated the following: 21 alive with no evidence of disease and with normal serum chemistry, 4 alive with disease (1 malignant PMTMCT with lung metastases). We conclude that most cases of mesenchymal tumor-associated OO, both in the present series and in the reported literature, are due to PMTMCT. Improved recognition of their histologic spectrum, including the presence of bone or osteoid-like matrix in otherwise typical cases and the existence of malignant forms, should allow distinction from other mesenchymal tumors. Recognition of PMTMCT is critical, as complete resection cures intractable OO. Immunohistochemistry and RT-PCR for FGF-23 confirm the role of this protein in PMTMCT-associated OO.

Adolescent↗

PubMed2004

Immunophenotypic differences between intestinal-type and low-grade papillary sinonasal adenocarcinomas: an immunohistochemical study of 22 cases utilizing CDX2 and MUC2.

Nonsalivary sinonasal adenocarcinomas can be divided into low-grade and high-grade tumors. The former are often papillary and the latter are usually of intestinal type, morphologically similar to metastatic colonic carcinoma. Antibodies to CDX2, a transcription factor gene highly specific for intestinal adenocarcinomas, MUC2, a mucin gene expressed in adenocarcinomas from various sites, and cytokeratins (CK) 7 and 20 were used to examine the two groups of tumors. Formalin-fixed, paraffin-embedded tissue from 22 sinonasal adenocarcinomas was reclassified into 9 high-grade intestinal-type, 3 high-grade nonintestinal, and 10 low-grade, predominantly papillary adenocarcinomas. Immunohistochemical staining was graded on a 0 to 4+ scale with 5% or greater tumor cell staining considered positive. Of the high-grade intestinal group, 78% demonstrated 4+ CDX2 positivity, with 44% MUC2 positive. Although 89% of this group was CK7 positive, the percent of staining was variable. A majority (67%) of the intestinal cases was 4+ CK20 positive. Almost every nonintestinal adenocarcinoma (90%) (low- and high-grade) was CK7 positive (7 of 9, 4+), without expression of any of the three colonic adenocarcinoma markers. The three high-grade nonintestinal tumors had the expression profile of the low-grade papillary group with the exception of focal MUC2 positivity in 1 case. Intestinal-type adenocarcinomas have an expression profile distinct from nonintestinal sinonasal adenocarcinomas. The former are similar, but not identical, to colonic adenocarcinomas. Immunohistochemical staining for CDX2, MUC2, and differential cytokeratins does not differentiate metastatic colorectal from primary sinonasal intestinal-type adenocarcinoma.

Adenocarcinoma, Papillary↗

PubMed2003

Salivary-type neoplasms of the breast and lung.

Salivary-type tumors occur in multiple sites in the human body, likely related to a basic structural homology between exocrine glands in these different anatomic areas. This paper reviews these salivary gland tumor types in breast tissue and lung. Salivary-type tumors of both breast and lung are relatively uncommon in comparison to their salivary gland counterparts. This may be attributable in part to lack of familiarity with these tumors in extra-salivary sites, and in part to histologic overlap with other primary and metastatic tumor types. Recognition of these entities is improving as the clinical and pathologic features are better delineated, and tumors are more accurately classified. Prediction of malignant behavior is not always possible in these unusual sites. In some instances, such as adenoid cystic carcinoma, behavior is known to differ considerably from that of analogous primary salivary gland tumors and in other instances there are simply too few reported cases to allow for adequate prognostication. In fact, more recent papers discuss the need to consider a spectrum encompassing benign and malignant lesions, in both breast and lung. Of course, some entities show clear-cut evidence of malignancy with documented potential for metastasis, others show bland features and well-reported benign behavior, and the less well-defined entities reside between these two extremes. The molecular pathology of salivary gland tumors has been reasonably well investigated in that location; however; there are few molecular studies devoted to salivary-type tumors of the breast and lung. This represents a potential area for future growth in further clarifying these tumors and their behavior.

Adenocarcinoma↗

PubMed2003

Glandular inclusions in inguinal hernia sacs: morphologic and immunohistochemical distinction from epididymis and vas deferens.

Glandular inclusions in inguinal hernia sacs may bear a striking resemblance to the epididymis or vas deferens. Misinterpretation as a transected functional structure may raise significant concerns regarding reproductive capability, even if encountered unilaterally. In a child, resolution of these concerns may be years away with the onset of puberty and documentation of normal sperm counts. CD10 has been shown to be present in Wolffian-type epithelium and to be absent in Mullerian-type epithelium. We hypothesized that an antibody to CD10 would react with vas deferens and epididymis and fail to react with hernia sac inclusions, most of which we thought were Mullerian duct-derived structures. Glandular inclusions in 29 hernia sacs from prepubertal males were classified histologically according to their resemblance to normal structures and analyzed for CD10 by immunohistochemistry. Inclusions resembling vas deferens had their external diameters measured and were also stained for smooth muscle actin. Thirty-one examples of normal vas deferens and 13 examples of normal epididymis were included for comparison. The inclusions were classified as vas deferens-like (9), epididymis-like (13), and Mullerian-like (7). CD10 reactivity was lacking in all vas deferens-like inclusions; their median external diameter was 0.6 mm. Of the epididymis-like inclusions, 7 of 13 were CD10 positive. The CD10-negative cases consisted of glands with well-defined stromal coats distinct from adjacent stromal coats. CD10-positive cases were more numerous, more tightly aggregated, and surrounded by less well-developed stromal coats that blended with adjacent coats. All seven Mullerian-like remnants were CD10 negative. All normal vas deferens and epididymis showed at least focal CD10 reactivity. CD10 positivity in all cases had a luminal membranous staining pattern. Both the vas deferens-like inclusions and the normal vas deferens showed strong smooth muscle actin positivity in their stromal coats. CD10 negativity and external diameter <1 mm are highly useful to distinguish vas deferens-like inclusions from true vas deferens. Epididymis-like inclusions are more problematic. Some react for CD10 and may represent aberrant Wolffian ductules. Others are CD10 negative, distinct from true epididymis, and may be of Mullerian differentiation. Mullerian-like remnants can be diagnosed on the basis of their limited number and scattered distribution. Lack of CD10 immunostaining corroborates this interpretation.

Adolescent↗

PubMed2002

Gleason scores of prostate biopsy and radical prostatectomy specimens over the past 10 years: is there evidence for systematic upgrading?

BACKGROUND: With the advent of the prostate specific antigen (PSA) assay, an increased detection rate of prostate carcinoma has ensued. This has been associated with a downward stage migration. In contrast, grade has shifted heavily toward moderate differentiation. The authors sought to test the hypothesis that such changes in grade in part may be because of trends among pathologists to upgrade similar specimens over time. METHODS: Two expert genitourinary pathologists regraded 23 prostate biopsies and 15 radical prostatectomy specimens during a 3-year period (1989-1991). Each pathologist then regraded 32 prostate biopsies and 15 radical prostatectomies from 1998 to 2000. For both time periods, each pathologist regraded only specimens that they personally had graded initially. All specimens were scored using the Gleason system, the predominant system used in describing prostate carcinoma grade. In evaluating original and regraded scores, the authors classified score changes between less than or equal to 6 and greater than or equal to 7 or between 7 and greater than or equal to 8 as significant because such changes have a high probability of altering clinical management. The results were analyzed using the two-tailed Fisher exact test. RESULTS: Of 23 prostate biopsies from 1989 to 1991, 10 of 23 (44%) had a clinically significant Gleason score change when regraded, whereas 2 of 15 (13%) radical prostatectomy specimens from the same period had a clinically significant Gleason score change. A significant change in the distribution of biopsy Gleason scores on regrading was observed (P < 0.04). In comparison, when the prostate biopsies from 1998-2000 were regraded, 10 of 32 (31%) had a clinically significant grade change. Radical prostatectomy specimens from the same period revealed 3 of 15 (20%) with a clinically significant grade change. After regrading the biopsies from 1989-1991, 8 of 23 (35%) of were upgraded, whereas 2 of 23 (9%) were downgraded. In comparison, of the biopsies with significant changes from 1998 to 2000, 3 of 32 (9%) were upgraded, whereas 7 of 32 (22%) were downgraded. Of the radical prostatectomy specimens with significant change, only 2 of 15 from each period were upgraded. Significant upgrading (P < 0.005) occurred only in the biopsy specimens from 1989 to 1991. CONCLUSIONS: The authors' data suggest that rates of upgrading and downgrading of biopsy specimens differ between the 1989-1991 cases and the 1998-2000 cases, with the 1989-1991 samples exhibiting a significant change toward higher grades. Although not excluding the possibility of a change in the biology of prostate carcinoma over time, these findings suggest that the apparent trend toward higher biopsy grades in part may be because of how pathologists interpret these specimens today as compared with 10 years ago. Therefore, outcome studies including a biopsy Gleason score from older specimens as a risk variable have a significant chance of being vulnerable to this phenomenon. Based on the authors' data, all such specimens should undergo rereview.

Biopsy, Needle↗

PubMed2002

Neuroectodermal neoplasms of the head and neck with emphasis on neuroendocrine carcinomas.

Tumors exhibiting neuroectodermal differentiation occur throughout the body, and the diverse tissues of the head and neck give rise to a wide assortment of these neoplasms. Neuroectodermal neoplasms may be divided into lesions showing primarily epithelial differentiation (Group I, neuroendocrine carcinomas) and a more diverse group (Group II) of nonepithelial neoplasms. This article reviews these neuroectodermal tumors of the head and neck with emphasis on the neuroendocrine carcinomas and their nomenclature. The author believes that with regard to Group I tumors, the older terminology of carcinoid, atypical carcinoid, and small cell carcinoma should be replaced by subclassifications of well-differentiated, moderately differentiated, and poorly differentiated neuroendocrine carcinoma. The latter category should be further subdivided into small cell and large cell variants. Neuroendocrine carcinomas, particularly the moderately differentiated subtype, are often underdiagnosed in the head and neck region. In the larynx, these tumors are the most common form of nonsquamous carcinoma. Poorly differentiated neuroendocrine carcinoma of small cell type is most common in the salivary glands but can occur elsewhere in the region. The large cell subtype of poorly differentiated neuroendocrine carcinoma has not been well documented in this region. However, the most likely candidate for this tumor category is the so-called sinonasal undifferentiated carcinoma. Group II tumors discussed include olfactory neuroblastoma, malignant melanoma, and Ewing's sarcoma. In addition, differential diagnostic problems related to Group I and II tumors are reviewed in detail. This article reviews and updates our understanding of neuroectodermal neoplasms arising in the head and neck. The focus is on tumors that exclusively involve this region or show a strong predilection to occur here.

Carcinoma, Neuroendocrine↗

PubMed2002

Interpretation of RET immunostaining in follicular lesions of the thyroid.

We applied monoclonal antibodies against RET and cytokeratin 19 (CK19) to the following tumor sections: classic papillary carcinoma (PC), 16; Hürthle-type PC (HPC), 1; sclerosing PC with nodular fasciitis-like stroma (SPC), 1; PC, follicular variant (FVPC), 12; follicular adenoma (FA), 9; Hürthle cell adenoma (HA), 4; Hürthle cell carcinoma (HC), 3; and follicular carcinoma (FC), 7. CK19+ tumors included 16 PCs, 1HPC, 1SPC, 11 FVPCs, 7 FAs, 4 FCs, and 1HC. RET+ tumors included 4 HAs, 3 HCs, 1HPC, 12 PCs, 7 FVPCs, and 2 FAs. Reverse transcriptase-polymerase chain reaction (RT-PCR) revealed a RET transcript in 6 Hürthle cell lesions. RET immunoreactivity is less sensitive and specific for PC than CK19. CK19 is useful for identifying PC, although only lesions with diffuse, intense staining should be considered positive. The detection of RET protein by immunohistochemical analysis was corroborated by the presence of the RET transcript by RT-PCR. Further study is warranted to determine whether this represents activation by gene fusion or some other mechanism in this subset of thyroid neoplasms.

Adenocarcinoma, Follicular↗

PubMed2002

Evaluation of surgical margins in anatomic pathology: technical, conceptual, and clinical considerations.

Virtually all anatomic pathologists are involved in the assessment of tissue margins in surgical procedures that are performed for malignant diseases. The natural tendency to view this process as uncomplicated has, in recent years, been countered by a body of literature on the biological milieu of the marginal zone. Moreover, empirical clinical information has shown that "negative" and "positive" marginal status has an imperfect correlation with risk of recurrent disease in several organ systems and in reference to various tumor types. Problems also remain regarding the optimal techniques for pathologic sampling of margins; the possible roles, if any, of adjuvant (eg, immunohistologic and "molecular") procedures for margin evaluation, and reporting motifs for selected surgical resections. This review considers conceptual data now available on surgical margins, provides a working approach to the generic assessment of marginal surfaces, and presents organ- and tumor- specific information pertaining to this area of practice.

Biomarkers, Tumor↗