No consensus exists regarding the optimal method for measuring tumor length or percentage of cancer on a core when there are two or more foci of prostate cancer in a single core separated by benign intervening stroma. One option is to measure discontinuous foci of cancer as if they were a single continuous focus. The other option is to add the measurements of the individual separate foci of cancer, ignoring the extent of the intervening benign prostate tissue. The authors conducted a study in which they searched the surgical pathology database at Johns Hopkins Hospital for outside consult cases of prostate needle biopsies reviewed between 2005 and 2010, when the patients came to Johns Hopkins for radical prostatectomy. Cases were restricted to those with a biopsy Gleason score of six in which there was at least 15 percent discordance between the outside consult and Johns Hopkins assessment in terms of the reported highest percentage of cancer per core per case. One hundred nine patients were identified, fulfilling the authors’ criteria for inclusion in their study. Seventy-nine patients showed the same Gleason score in the radical prostatectomy, and 30 had an upgrade to a Gleason score of seven or more. Including all cases (scores six, seven, and eight at radical prostatectomy), there was no significant association between the maximum percentage of cancer per core with organ-confined disease or risk of positive surgical margins, regardless of whether the cores were measured at Hopkins or at outside institutions. For cases with no upgrade at radical prostatectomy, the differences between the maximum percentage of cancer per core per case recorded at Hopkins and the outside institutions ranged from 15 percent to 80 percent, and the mean and median differences were 35 percent and 30 percent, respectively. The maximum percentages of tumor involvement on a core per case given at Hopkins more strongly correlated with the presence of organ-confined disease (P=.004) compared with the percentages given at the outside institutions (P=.027). Surgical margin positivity was also associated with maximum percentages of tumor involvement per core given at Hopkins (P=.004), whereas the outside percentages were not significant predictors of margin status (P=.2). In a multivariable analysis, maximum percentage of cancer per core per case measured at Hopkins, which included intervening benign prostate tissue in the measurement, was more predictive of stage and margins than ignoring intervening benign tissue. This study demonstrated that for prostate cancer in which the needle biopsy grade is representative of the entire tumor, quantifying cancer extent on biopsy by measuring discontinuous cancer on biopsy from one end to the other, as opposed to “collapsing” the cancer by subtracting the intervening benign prostate tissue, correlates better with organ-confined disease and risk of positive margins.
Karram S, Trock BJ, Netto GJ, et al. Should intervening benign tissue be included in the measurement of discontinuous foci of cancer on prostate needle biopsy? Correlation with radical prostatectomy findings. Am J Surg Pathol. 2011;35(9):1351–1355.
Correspondence: Dr. Jonathan I. Epstein at email@example.com
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The authors examined borderline estrogen receptor-positive cancers, defined as having one percent to 10 percent positivity by immunohistochemistry, to determine whether they show the same global gene-expression pattern and high ESR1 mRNA expression as estrogen receptor (ER)-positive cancers or whether they are more similar to ER-negative cancers. They determined estrogen receptor status by immunohistochemistry in 465 primary breast cancers and with the Affymetrix U133A gene chip. The authors compared expressions of ESR1 mRNA and a 106-probe set ER-associated gene signature score between ER-negative (n=183) cancers and one percent to nine percent (n=25), 10 percent (n=6), and greater than 10 percent (n=251) ER-positive cancers. They also assessed molecular class using the PAM50 classifier and plotted survival by ER status. The authors found that among the one percent to nine percent, 10 percent, and greater than 10 percent ER immunohistochemistry-positive patients, 24 percent, 67 percent, and 92 percent were also positive by ESR1 mRNA expression. The average ESR1 expression was significantly higher in the 10 percent or greater ER-positive cohorts compared with the one percent to nine percent or ER-negative cohorts. The average ER gene signature scores were similar for the ER-negative and one percent to nine percent immunohistochemistry-positive patients and were significantly lower than in the 10 percent or greater ER-positive patients. Among the one percent to nine percent ER-positive patients, eight percent were luminal B and 48 percent were basal like. Among the 10 percent of ER-positive patients, 50 percent were luminal. The overall survival rate of one percent to nine percent ER-positive patients with cancer was between those of patients in the 10 percent or greater ER-positive and ER-negative groups. The authors concluded that a minority of the one percent to nine percent immunohistochemistry ER-positive tumors show molecular features similar to those of ER-positive, potentially endocrine- sensitive tumors, whereas most show ER-negative, basal-like molecular characteristics. The safest clinical approach may be to use both adjuvant endocrine therapy and chemotherapy in this rare subset of patients.
Iwamoto T, Booser D, Valero V, et al. Estrogen receptor (ER) mRNA and ER-related gene expression in breast cancers that are 1% to 10% ER-positive by immunohistochemistry. J Clin Oncol. 2012;30:729–734.
Correspondence: Dr. Lajos Pusztai at lpusz firstname.lastname@example.org
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The ARID1A gene has been identified as a novel tumor suppressor in ovarian clear cell carcinoma. The prognostic significance of the loss of ARID1A expression is not known. The authors conducted a study to evaluate whether ARID1A is a prognostic factor for progression, survival, and chemoresistance in ovarian clear cell carcinoma. They enrolled in their study 60 patients who were surgically treated for primary ovarian clear cell adenocarcinoma. The authors examined surgical specimens for ARID1A protein expression by immunohistochemistry. They investigated correlations between the loss of ARID1A expression and clinicopathological characteristics, prognosis, and chemosensitivity. The authors identified loss of ARID1A expression in nine of 60 (15 percent) ovarian clear cell carcinoma samples. Loss of ARID1A staining intensity (0+) was more frequently found in cells of clear cell carcinomas than in high-grade serous carcinomas (P<.01). Loss of ARID1A expression was significantly correlated with advanced FIGO stage and high CA125 levels (P=.02; 0.01). No significant correlations were noted between loss of ARID1A expression and patient age, status of residual tumor, Ki-67 labeling index, or status of endometriosis. Loss of ARID1A correlated with shorter progression-free survival of patients with clear cell carcinomas treated with platinum-based chemotherapy (P<.01). And loss of ARID1A expression tended to correlate with shorter overall survival rates in patients with ovarian clear cell carcinomas treated with platinum-based chemotherapy. When data were stratified for multivariate analysis, only the loss of ARID1A expression remained a significant (P=.03) predictor of reduced progression-free survival. Of the 60 patients with ovarian clear cell carcinomas, 14 had measurable residual tumor after primary cytoreductive surgery. Tumors with loss of ARID1A expression were more likely to be chemoresistant than tumors with positive ARID1A expression (100 versus 40 percent; P=.04). The authors concluded that their study demonstrated that loss of ARID1A in ovarian clear cell carcinoma is a negative prognostic factor in patients treated with platinum-based chemotherapy. Measurement of ARID1A expression may be a method to predict resistance to platinum-based chemotherapy in patients with ovarian clear cell carcinoma.
Katagiri A, Nakayama K, Rahman MT, et al. Loss of ARID1A expression is related to shorter progression-free survival and chemoresistance in ovarian clear cell carcinoma. Mod Pathol. 2012;25:282–288.
Correspondence: Dr. K. Nakayama at email@example.com
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Merkel cell carcinoma of the skin is a malignant neuroendocrine tumor for which prognostic criteria are a matter of dispute. No predictor is available in stage I–II tumors. The authors conducted a study of potential predictors of Merkel cell carcinoma in which they collected clinical and followup data from 70 Merkel cell carcinomas of the skin. The same cases were studied for p63 expression by immunohistochemistry and reverse-transcription PCR (RT-PCR), and for TP63 gene status by fluorescence in situ hybridization (FISH), as well as for Merkel cell polyomavirus by PCR. Stage emerged as a significant prognostic parameter (P=.008). P63 expression, detected in 61 percent (43 of 70) of cases by immunohistochemistry, was associated with decreased overall survival (P<.0001) and disease-free survival (P<.0001). Variable expression patterns of the various p63 isoforms were found only in cases immunoreactive for p63. In these latter lesions, at least one of the N-terminal p63 isoforms was detected, and TAp63α was the most frequently expressed isoform. TP63 gene amplification was observed by FISH in only one case. Merkel cell polyomavirus DNA sequences were detected in 86 percent (60 of 70) of Merkel cell carcinomas and did not emerge as a significant prognostic parameter. Merkel cell carcinoma cases at low stage (stage I–II) represented more than half (40 of 70; 57 percent) of cases. Clinical course was uneventful in 25 of 40 of those cases, while 15 patients died of tumor (10 of 40) within 34 months or were alive with disease (five of 40) within 20 months. A very strict correlation was found between evolution and p63 expression (P<.0001). Data indicate that p63 expression is associated with a worse prognosis in patients with Merkel cell carcinoma. In localized tumors, it represents the single independent predictor of clinical evolution.
Asioli S, Righi A, de Biase D, et al. Expression of p63 is the sole independent marker of aggressiveness in localised (stage I–II) Merkel cell carcinomas. Mod Pathol. 2011; 24(11):1451–1461.
Correspondence: Dr. S. Asioli at firstname.lastname@example.org
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The authors conducted a study to examine the feasibility and clinical significance of guidelines on nodal assessment in patients with rectal cancer who were treated with neoadjuvant radiation. The study involved patients with rectal cancer who were treated with curative surgery from 1991 to 2003. Number of lymph nodes assessed was compared between patients who received neoadjuvant therapy and surgery (NEO) and patients who underwent surgery alone. The authors also analyzed the impact of node retrieval on node positivity and disease-specific survival in NEO patients. A total of 708 patients were identified for the study, 429 (61 percent) of whom were in the NEO group. These patients had significantly fewer nodes assessed than patients who underwent surgery alone (unadjusted mean, 10.8 versus 15.5; adjusted mean difference, -5.0 nodes; P<.001). In the NEO group, 63 percent of patients had fewer than 12 nodes retrieved (P<.001 versus surgery alone). The proportion of patients diagnosed with node-positive disease in the NEO group was significantly and monotonically associated with the number of lymph nodes retrieved, with no plateau in the relationship. Fewer nodes retrieved was not associated with inferior disease-specific survival. The authors concluded that in a tertiary cancer center, the 12-lymph node threshold was not relevant and often not achievable in patients with rectal cancer treated with neoadjuvant therapy. A lower lymph node count after neoadjuvant treatment was not associated with understaging or inferior survival. Although the authors recognize the critical importance of careful pathologic examination and adequate nodal staging, they challenge the relevance of lymph node count in clinical practice and as a quality indicator in rectal cancer.
Govindarajan A, Gönen M, Weiser MR, et al. Challenging the feasibility and clinical significance of current guidelines on lymph node examination in rectal cancer in the era of neoadjuvant therapy. J Clin Oncol. 2011;29: 4568–4573.
Correspondence: Dr. Garrett M. Nash at email@example.com
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Poorly differentiated carcinomas of the thyroid are conceptually situated between well-differentiated (papillary or follicular) carcinomas and anaplastic thyroid carcinomas. Although the morphologic criteria for poorly differentiated tumors are well defined, it is not clear how much of a poorly differentiated area besides a well-differentiated component in a given tumor is required to allow such a diagnosis. The authors identified 42 patients suffering from thyroid carcinoma who had an adverse clinical outcome. They added 50 patients with follicular carcinoma as controls. The authors analyzed poorly differentiated areas by applying the Turin criteria of poorly differentiated carcinomas. These criteria consist of the presence of a solid/trabecular/insular growth pattern, lack of nuclear features of papillary carcinoma, and presence of convoluted nuclei or tumor necrosis or three or more mitoses per 10 high-power fields. Using a cutoff value of 10 percent of poorly differentiated areas per examined tumor surface, the authors identified 35 poorly differentiated carcinomas. Despite using a threshold of 10 percent of the tumor area as poorly differentiated, the survival data in a Kaplan-Meier analysis were significantly worse than those for the control group (P<.001) and did not differ from tumors with a poorly differentiated area greater than 50 percent. In a multivariate analysis that analyzed age, gender, tumor stage, and poorly differentiated area greater than 10 percent against survival data, the only consistent significant factor was poor differentiation (P<.001). The authors concluded that because even slight amounts of poorly differentiated areas (10 percent or more) in a thyroid carcinoma affect prognosis significantly, the presence of such areas may be worth reporting in thyroid carcinomas.
Dettmer M, Schmitt A, Steinert H, et al. Poorly differentiated thyroid carcinomas: How much poorly differentiated is needed? Am J Surg Pathol. 2011;135;1866–1872.
Correspondence: Dr. Matthias Dettmer at firstname.lastname@example.org
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Anatomic pathology abstracts editors: Michael Cibull, MD, professor and vice chair, Department of Pathology and Laboratory Medicine, University of Kentucky College of Medicine, Lexington; Rouzan Karabakhtsian, MD, assistant professor of pathology and laboratory medicine, University of Kentucky College of Medicine; and Thomas Cibull, MD, dermatopathologist, Evanston Hospital, NorthShore University HealthSystem, Evanston, Ill.