Use of modifying phrases in surgical pathology reports: is there a different understanding between pathologists and treating physicians?

When not all the histopathologic and clinical features necessary for a pathology diagnosis are present in a particular specimen, pathologists may use modifying phrases to convey various degrees of certainty, e.g., "consistent with…" and "suggestive of…." However, it is unclear whether pathologists use such phrases consistently or whether treating physicians fully understand their intended meaning. A questionnaire concerning six common modifying phrases ("consistent with, suggestive of, suspicious for, highly consistent with, highly suggestive of, some features of") was sent to all physicians from a single institution who either issued or routinely received surgical pathology reports. Physicians were asked to rank their understanding of each phrase on a printed scale between 1 ("no evidence of") and 10 ("diagnostic of"). One hundred sixty physicians (74.3%) responded. Despite wide variation, there was a hierarchy (from more to less diagnostic): highly consistent > highly suspicious > consistent > suspicious > suggestive > some features (p < 1 × 10-7). There were no significant differences between pathologists and treating physicians (p = 0.72) or attendings and residents (p = 0.9). Pathologists and treating physicians share an overall common understanding of their hierarchical relationship, albeit with wide ranges. Based upon our results, we propose to use only three qualifying phrases to convey the degree of certainty for a particular diagnosis: "suggestive of" (> 25 ≤ 50% certainty), "suspicious for" (> 50 ≤ 75%), and "consistent with" (> 75%). The phrase "no evidence of" should probably be used only when there is ≤ 5% confidence in a diagnosis, and conversely, "diagnostic of" should probably be used only when there is ≥ 95% confidence in a diagnosis.

Prognostic value of various morphometric measurements of tumour extent in prostate needle core tissue.

AIMS: Predicting prostatic cancer patients' outcome is a major objective for clinicians and patients. Several nomograms are currently implemented prior to treatment to help predict clinical and pathological outcome. The aim of this study was to investigate the prognostic significance of morphometric measurements of cancer on the needle biopsy specimen in relation to the final pathological stage or the biochemical failure status following radical prostatectomy, and to determine which measurement of tumour length in cases with discontinuous foci of cancer (DFC) is most reliably reflective of the pathological stage. METHODS AND RESULTS: Of the 100 patients included in this study, 34% had high-stage disease (pT >or= 3 and/or pN1) and 16% experienced biochemical recurrence. The analysis showed that fraction of positive cores, total percentage of cancer and both total and greatest millimetric cancer lengths were the variables most closely associated with pathological stage and biochemical failure status. CONCLUSIONS: This study confirms the prognostic value of recording tumour extent in prostatic needle biopsy reporting. However, the results are inconclusive in determining the best method to record tumour length in cores with DFC and larger studies are needed to answer this question fully.

Heterotransplantation of a human prostatic adenocarcinoma cell line in nude mice.

Nude mice of NIH/Swiss background were utilized for the heterotransplantation of a tissue culture cell line derived from a human prostate adenocarcinoma metastatic to the brain. These cells, which had been grown in vitro for 13 passages, formed solid tumors when injected s.c. into nude mice. The cell line DU 145 has been passaged 60 times in vitro over a period of 18 months. Tumors removed from the mice were serially transplanted to additional mice and reestablished in vitro. Light-microscopic analysis of the tumor grown in nude mice revealed a strong similarity to the patient's metastatic tumor. The ultrastructure of the tumor cells propagated in nude mice was compared to that of the original human tumor cells and to the tissue culture cells, both before and after passage in nude mouse. No major differences were detected. Karyotypic analysis of the tumor cells grown in vitro before mouse passage, grown in nude mouse, and grown in vitro after mouse passage indicated chromosomal identity and consistent marker chromosomes: three large acrocentric chromosomes and metacentric minute chromosomes.

Predicting tumor failure in prostate carcinoma after definitive radiation therapy: limitations of models based on prostate-specific antigen, clinical stage, and Gleason score.

In this report, we use new patient data to test three popular models developed to predict the outcome of definitive radiation therapy. The data come from 240 men with localized prostate cancer and who were treated with definitive radiation therapy at a community hospital. All three models tested were based on the three commonly available variables of pretreatment prostate-specific antigen (PSA), Gleason score, and tumor stage, and we used the Cox proportional hazards model and the logistic regression model to relate these variables to outcome. We discovered that in our data, the optimal way to use pretreatment PSA was as natural log(PSA), the optimal way to use T stage was in three categories: T1 and T2, T3, and T4, and that the optimal use of Gleason score was as <7 versus > or =7. Nevertheless, models confined to the optimal use of these three variables leave much uncertainty about important outcomes, such as the probability of relapse within 5 years.

The dynamics of prostate-specific antigen after definitive radiation therapy for prostate cancer.

We report the use of an exponential model for capturing the dynamics of serial measurements of prostate-specific antigen (PSA) made just before and after definitive radiation therapy of localized prostate cancer. Our study patients consisted of 164 men treated at a community hospital and without use of adjuvant hormonal therapy, and we had a mean of 5 years follow-up. We found that the model fits allowed us to condense PSA dynamic information into four parameters, including the initial pretreatment value of PSA, and three of these related significantly to subsequent outcome. The model also provided greater understanding of the prognosis of men with rising PSA after radiation therapy. Specifically, two of the model's parameters allowed us to compare the PSA status of these men to those with hormone-refractory disease, and we discovered that at the time of "biochemical relapse," there is a broad spectrum in expected probability of imminent death as well as in time to an adverse outcome. Thus, the model provides information that allows one to stratify men with rising PSA into a continuous spectrum from low to high risk for an adverse outcome. We believe these results show that exponential models have the potential for providing useful clinical information about men with rising PSA after definitive radiation therapy and that they could help us decide when further therapy is needed. Therefore, we recommend further study and development of these models as part of clinical research protocols involving radiation therapy of localized prostate cancer.

A prognostic score for hormone-refractory prostate cancer: analysis of two cancer and leukemia group B studies.

Previously, we have shown that serial measurements of prostate-specific antigen (PSA) in hormone-refractory prostate cancer (HRPC) can be used to calculate an average relative velocity (rva) of PSA. Together, the level of PSA and the rva formed a two-variable model for survival time that worked at any time during the course of HRPC. Here, we have added serial measurements of hemoglobin and weight to test whether they improve the prior model based on PSA alone. Data from two Cancer and Leukemia Group B studies (9181 and 9182) on HRPC were combined to study the relationship between survival and serial measurements of PSA, serum hemoglobin, and patient weight. Altogether, there were 348 patients who could be evaluated. We used the Cox proportional hazard model for survival time with the interval censored method to accommodate time-dependent covariates, and tests for significance were two sided. Log (PSA), rva, log (hemoglobin), and log [weight (in kg)] were all significantly related to survival time during the course of HRPC (P < 3.0 x 10(-5)). Together, they formed a prognostic score based upon the relative hazard. Higher values of this score implied higher probability of death as the next observed event. Serial measurements of PSA, hemoglobin, and weight provide a prognostic score that can be applied continuously during the course of HRPC. Changes in the score may provide a reproducible measure of treatment effect.

Disparate results between proliferation rates of surgically excised prostate tumors and an in vitro bioassay using sera from a positive randomized controlled trial.

In vitro bioassay has been used extensively to test the effects of culturing cancer cells in sera from humans participating in dietary interventions, i.e, studies of modified intake of nutrients for the purpose of reducing cancer risk or progression. It has been hypothesized that cell proliferation rates determined by the in vitro bioassay indicate whether modification of dietary intake could decrease cancer cell growth in vivo. It has been suggested, however, that the in vitro bioassay may not correlate with tumor cell proliferation rates in prostate cancer. We investigated the concordance of cell proliferation rates from surgically excised prostate tumor tissue with the in vitro bioassay using sera from matched patients. We used samples from an earlier randomized clinical trial that showed that supplementation with flaxseed significantly inhibited prostate cancer cell proliferation rates in vivo as indicated by Ki67 staining in tumor specimens. Proliferation rates of LNCaP, DU145 and PC3 cell lines cultured in 10% human sera from participants in the flaxseed trial were determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Spearman's Rho correlation coefficients (ρ) indicated no association between Ki67 staining in prostate tumors and the in vitro bioassay for the three cell lines. These disparate findings suggest that the in vitro bioassay may not provide an accurate assessment of the environment in vivo.

Vitamin D and prostate cancer: a prediagnostic study with stored sera.

This study evaluates the risk of prostate cancer in relation to serum levels of the major vitamin D metabolites, 25-hydroxyvitamin D (25-D3) and 1,25-dihydroxyvitamin D (1,25-D). Between 1964 and 1971, more than 250,000 serum samples were collected from members of the Kaiser Permanente Medical Care Plan in Oakland and San Francisco and stored for future use. Levels of 25-D and 1,25-D were measured in samples from 90 black and 91 white men diagnosed with prostate cancer before December 31, 1987 and controls individually matched on age, race, and day of serum storage. Mean serum 1,25-D was 1.81 pg/ml lower in cases than in matched controls (P = 0.002). Risk of prostate cancer decreased with higher levels of 1,25-D especially in men with low levels of 25-D. However, mean 25-D was not significantly different in cases and controls. The association of lower 1,25-D with prostate cancer was found in men above the median age of 57 years at serum storage but not younger men and was similar in black and white men. In men > or = 57 years of age, 1,25-D was an important predictor of risk for palpable and anaplastic tumors but not for tumors incidentally discovered during surgery to treat the symptoms of benign prostatic hyperplasia or well differentiated tumors.

Extramedullary hematopoiesis in the prostate.

A case of bone marrow myelofibrosis with extramedullary hematopoiesis in the prostate gland is described. This 75-year-old man had an 8-year history of myelofibrosis, massive hepatosplenomegaly, and progressive anemia and a 5-year history of bladder outlet obstruction symptomatology. Transurethral resection of prostate was performed, and light microscopic examination of the prostatic chips revealed a diffuse distribution of atypical megakaryocytes, immature granulocytes, and normoblasts in the prostatic stroma. The prostatic glandular epithelium was uninvolved. Immunostaining for hemoglobin in erythroid precursors and a chloroacetate esterase stain for granulocytic precursors were useful in confirming the diagnosis and in defining the extent of prostatic involvement. Extramedullary hematopoiesis is a rare process in the prostate gland, but it should be included in the differential diagnosis of cellular prostatic stromal lesions, particularly when atypical giant cells are observed.

Systemic kappa light-chain deposition. An ultrastructural and immunohistochemical study.

This report describes the pathology of kappa light-chain deposition in a 55-year-old patient who presented with respiratory insufficiency and hepatomegaly. Biopsies of lung and liver showed PAS-positive deposits which did not stain with congo red, crystal violet, or thioflavin-T. By indirect immunoperoxidase techniques, the deposits were composed of kappa light-chain immunoglobin. Electron microscopy revealed granular and fibrillar electron-dense material which lacked the characteristics of amyloid. Subsequent clinical studies showed this patient had a plasma cell dyscrasia. These data show that kappa light-chain deposition is not limited to the kidney, and that the first manifestation of a plasma cell dyscrasia may be systemic deposits of light chain. These deposits can be distinguished from amyloid by their immunochemical, tinctorial, and ultrastructural appearance.

Histologic grade, DNA ploidy, and intraglandular tumor extent as indicators of tumor progression of clinical stage B prostatic carcinoma. A direct comparison.

Histologic grade, DNA ploidy, and percentage tumor area were assessed in prostatectomy specimens from 73 patients with clinical stage B adenocarcinoma of the prostate and analyzed for their value as predictors of tumor progression. Further, the relationship between percentage tumor area and DNA ploidy was studied. Percentage tumor area was the indicator most strongly associated with the likelihood of tumor extension beyond the capsule of the prostate and of tumor progression as assessed in a logistic regression model. Grade was slightly superior to percentage area in predicting time to progression in a Cox model analysis. Increasing percentage tumor area was associated with an increased likelihood of aneuploidy. Little additional predictive ability was obtained with the concurrent use of two indicators in multivariate analysis, suggesting a high degree of interrelatedness of percentage tumor area, histologic grade, and DNA ploidy. DNA ploidy was not an independent predictive factor, and from a practical standpoint histologic grade and percentage tumor area were more important predictors of tumor progression than DNA ploidy.

Renal cell carcinoma with rhabdoid features.

Neoplasms with rhabdoid features have been reported at many anatomic sites. In the kidney, rhabdoid tumors are typically found in children, whereas only rare examples have been reported in adults. Little is known of renal cell carcinomas (RCCs) that exhibit rhabdoid features. The objective of this study was to determine the incidence of RCC with rhabdoid attributes and characterize the histologic, immunophenotypic, and ultrastructural features by retrospective analysis of 480 consecutively identified cases of RCC in radical nephrectomy specimens. Immunohistochemical evaluation was performed in cases with rhabdoid foci using a panel of antibodies to pancytokeratin (pan-CK), CK7, CK20, epithelial membrane antigen (EMA), S-100 protein, desmin, vimentin, neuron-specific enolase (NSE), muscle-specific actin (MSA), smooth muscle actin (SMA), human melanoma, black-45 (HMB-45), and glial fibrillary acidic protein (GFAP). Electron microscopy was also performed in selected cases. The presence and extent of rhabdoid foci in relation to pathologic stage and grade were assessed. Twenty-three of 480 cases of RCC (4.7%) exhibited rhabdoid features. The 23 patients were all adults with a mean age of 61.8 years (age range, 33-84 yrs). Fifteen of the patients were men and eight were women. Histologically, the rhabdoid foci were typified by sheets and clusters of variably cohesive, large epithelioid cells with vesicular and often eccentric nuclei, prominent nucleoli, and large, paranuclear intracytoplasmic hyaline globules (inclusions). The presence of these rhabdoid features was related to high histologic Fuhrman grade of the nonrhabdoid carcinoma component, with an incidence of 0 of 84 grade I cases, eight of 300 grade 2 cases (2.6%), six of 70 grade 3 cases (8.9%), and nine of 26 grade 4 cases (34.6%; p = 3 x 10(-9)). The rhabdoid foci were all high grade. The presence of rhabdoid foci was also found in higher stage carcinomas. A total of 52% (12 of 23) of RCC cases with rhabdoid features exhibited extrarenal extension compared with 28% (24 of 92) of contemporary RCCs without rhabdoid features (p = 0.03). The size of the rhabdoid component ranged from 1 mm to more than 2 cm and comprised 1% to 50% of the renal mass. Immunoreactivity for vimentin (100%), NSE (79%), and panCK (56%) was present in the majority of cases. Substantial percentages of cases were immunopositive for EMA (47%) and S-100 protein (37%), with minimal to no immunohistochemical reactivity for CK7 (5%), SMA (5%), CK20 (0%), desmin (0%), MSA (0%), HMB-45 (0%), and GFAP (O%). A distinctive globular, paranuclear reaction pattern was found for the cytokeratin, EMA, and vimentin immunostains. Ultrastructurally, the rhabdoid cells had paranuclear intermediate filament aggregates or paranuclear condensation of organelles, often associated with peripheral vacuolization. Adult RCCs may harbor a rhabdoid component, and these neoplasms can be regarded as "composite" tumors. Rhabdoid elements are important to identify because of their high-grade nature, and association with high stage. Adult RCC with rhabdoid elements should be distinguished from pure rhabdoid tumors of kidney, in light of their clinicopathologic differences. Rhabdoid differentiation in adult renal cell carcinoma may represent clonal divergence and/ or evolution, and emergence of a particularly aggressive element.

Relation of temporal creatine kinase-MB release and outcome after thrombolytic therapy for acute myocardial infarction. TAMI Study Group.

Measuring biochemical marker release after acute myocardial infarction helps in estimating infarct size and prognosis. We sought to relate in-hospital outcomes and curve-fitted creatine kinase (CK)-MB variables after thrombolysis. We measured CK-MB mass initially and at 30 and 90 minutes, and at 3, 8, and 20 hours after thrombolysis in 130 patients also undergoing cardiac catheterization at 90 minutes and at 5 to 7 days. Data were fitted, and maximums and curve areas calculated. CK-MB maximums related to infarct location (p = 0.014) and time to therapy (p = 0.002); curve area did not. Neither maximums nor curve area related to Thrombolysis in Myocardial Infarction trial flow grade at 90 minutes. Maximums related to ejection fraction at 90 minutes (p = 0.0004) and at 5 to 7 days (p = 0.0014), as did curve area (p = 0.0076 and 0.030, respectively). Maximums related to infarct zone function at 90 minutes (p = 0.024) and at 5 to 7 days (p = 0.042); curve area related only at 90 minutes (p = 0.027). Both maximums and curve area predicted congestive heart failure (p = 0.008 and p = 0.042, respectively) and a composite of congestive heart failure or death (p = 0.004 and p = 0.047, respectively); however, after adjusting for maximums, curve area no longer predicted congestive heart failure (p = 0.92). Maximums predicted the composite outcome after adjustment for curve area, and showed a trend toward predicting congestive heart failure (p = 0.089). We conclude that CK-MB maximums relate to infarct zone function, left ventricular function, and in-hospital outcomes after thrombolysis for acute myocardial infarction.

Prostate cancer and chip specimens: complete versus partial sampling.

During a nine-year period, 850 routine prostatectomy specimens were examined by placing all of the tissue in blocks for complete microscopic examination. Of these specimens, 711 were obtained from patients in whom cancer had not been diagnosed previously; 61 cancers were found in this group, with 49 of these cancers from glands that had not been considered questionable on clinical examination. Review of the material suggests that for optimal partial sampling of transurethral prostatectomy specimens, five blocks should be submitted; this method is economical and will detect approximately 90 per cent of cancers, including all those consisting predominantly of Gleason pattern 4 or 5, all progressive cancers, and all cancers identified clinically as stage 3 or 4. The detection of all focal cancers probably requires examination of all tissue, but such detection may be unimportant to the patient's prognosis.

The ratio of prostate chips with cancer: a new measure of tumor extent and its relationship to grade and prognosis.

The ratio of chips with cancer to the total number of chips was studied in 118 patients with prostate cancer who underwent transurethral prostatectomy. We found that this ratio is a prognosticator closely associated to the stage of tumor (local or extensive) and to the chance of death from prostate cancer. Stage, the ratio of positive chips and the Gleason histologic score are all closely tied one to another, and it is unclear from this initial study whether these variables provide independent or additive prognostic information. Nevertheless, the ratio of positive chips shows far better interobserver agreement than does the Gleason score, and in patients with the most common predominant score of three, it can separate most of those with localized disease from most of those with extensive disease. Thus the ratio shows promise as a reliable predictor of stage of disease and of long-term failure, and hence it may help in the choice of patients for curative surgery.

Intraglandular tumor extent and prognosis in prostatic carcinoma: application of a grid method to prostatectomy specimens.

The extent of tumor in prostatectomy specimens was determined by a grid method in 117 patients with prostatic adenocarcinoma. A plastic strip or ruler with squares of 3.0 mm was used, and the ratio of squares overlying carcinoma to the total number of squares overlying prostate tissue was calculated. This grid ratio, which represents an estimate of the percentage of the prostate involved by tumor, was a significant prognosticator closely tied to the likelihood of tumor progression and to survival time, as assessed by logistic regression analysis and a proportional hazard model. The grid ratio was better than histologic grade in predicting tumor progression and patient survival; also, the ratio was more objective than histologic grade as judged by interobserver agreement values. Only slight improvement in prognostication was obtained with concurrent use of both extent and grade. The grid ratio method was slightly better in predicting tumor progression and patient survival than a second method of assessing the percentage of prostatic tissue involved by tumor, the pathologist's percentage estimate. These results indicate that it is important to quantitate tumor extent within prostatectomy specimens; such quantitation need not require step-sectioning of the entire prostate and an expensive and time-consuming method such as computerized morphometrics but rather may be performed by a simple estimate of the percentage of the prostate involved by tumor. Reporting of histologic grade and tumor extent in the prostate gland is recommended as both appear to be important in identifying those patients at risk for a poor outcome after prostatectomy for prostatic carcinoma.

Asbestos body concentrations in human lung: predictions from asbestos body counts in tissue sections with a mathematical model.

A mathematical model for predicting the concentration (Nv) of asbestos bodies (AB) in human tissue from the count (No) of these bodies in planar tissue sections is presented. The result is the equation Nv = No/[0.54 X A X (La + t)], giving the concentration of AB in numbers per gram of wet lung tissue. La, the average length (in microns) of the AB, is specific for each case; A is the area (square millimeters) of the tissue counted, and t is the thickness of the section (in microns). This equation fits experimental digestion results to a multiplicative error factor of less than 3. When an estimate of La, such as 51.6 microns, is used, the equation is less accurate but probably sufficiently accurate for the screening of lung specimens.

Basaloid-squamous carcinoma of the tongue, hypopharynx, and larynx: report of 10 cases.

Ten cases of an unusual form of carcinoma involving the mucosa and underlying tissue of the tongue, hypopharynx, and larynx are described. All ten of the tumors were evaluated by light microscopy; five were also studied by electron microscopy. The major histopathologic feature is carcinoma with a basaloid pattern in intimate association with squamous cell carcinoma, carcinoma in situ, or focal squamous differentiation. The basaloid tumor consists of small crowded cells with hyperchromatic nuclei, scant cytoplasm, small cystic spaces, and foci of tumor necrosis. Prominent hyalinosis is evident. Ultrastructurally, the basaloid epithelial cells possess rare tonofilaments and varying amounts of desmosomes. The cystic spaces contain either loose stellate granules or replicated basal lamina arranged in parallel stacks or globoid masses. This unique tumor was found to be highly malignant, with histologically proved metastases in 80 per cent of the cases. Most of the patients were treated by radical surgery supplemented with radiation and/or chemotherapy. It is concluded that tumors with these characteristic features constitute a distinct histopathologic entity, not previously described, for which basaloid-squamous carcinoma is an appropriate term.

Intercellular junctions and tumor stage in small cell carcinoma of the lung.

The authors have studied the ultrastructural features of 52 cases of oat cell carcinoma of the lung and have related their observations to tumor stage and patient survival. Only the type of cell junctions seems to be of prognostic importance. Tumors with intermediate junctions--and especially those with desmosomes--have a more localized stage and may be resectable to result in longer survival than expected for oat cell carcinomas without junctions. For example, in the authors' series the median survival periods for those with no identifiable junctions, intermediate junctions, or desmosomes were 6.4, 8.2, and 11.3 months, respectively. Nevertheless, this ultrastructural subclassification is not as effective as that obtained from careful clinical staging.

Correlating architectural disorder and cytologic atypia in Clark (dysplastic) melanocytic nevi.

Histological architecture is very important in the pathological diagnosis of Clark (also known as atypical or dysplastic) melanocytic nevi. However, few studies have attempted to quantify architectural features or to correlate them directly with cytology. In 166 consecutive Clark nevi, the presence or absence of the following features in the intraepidermal or junctional component was recorded: (1) Architecture: circumscription, symmetry, cohesiveness of nests, suprabasal melanocytes, confluence, and single-cell proliferation; (2) Cytology of melanocytes: round/euchromatic nuclei, nuclear enlargement, cell enlargement, and prominent nucleoli. Each criterion was given a value of 0 or 1, and a summation score was obtained for both architecture and cytology in each case. The chi-square test was used to determine the significance of relationships among these parameters. The degrees of architectural disorder and of cytologic atypia were positively correlated (P = .026). Scores for both parameters were distributed over a wide range of values and were concentrated toward the low-middle portion of the spectrum. Several particular architectural and cytologic variables showed significant interdependence. Clark nevi exhibit a broad spectrum of architectural disorder and cytologic atypia, which, according to our data, generally are closely related features. Because some cases displayed a relatively high score for one parameter but a low score for the other, quantification of both parameters permits a more complete histopathologic evaluation of these lesions and may provide additional information for their clinical management.