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  Anatomic Abstracts






November 2007

Michael Cibull, MD
Melissa Kesler, MD

Lymph node evaluation and survival after curative resection of colon cancer
Positive-block ratio in radical prostatectomy specimens as a predictor of PSA recurrence
Mucin profiles in signet-ring cell carcinoma
Extranodal marginal zone B-cell lymphomas of the ocular adnexa
Immunohistochemical analysis of langerin in LCH and pulmonary inflammatory and infectious diseases

bullet Lymph node evaluation and survival after curative resection of colon cancer

The number of lymph nodes evaluated for cancer involvement may be a measure of quality in colon cancer care and appears to be inadequate in most patients treated for the disease. The authors conducted a systematic review of the association between lymph node evaluation and oncologic outcomes in patients with colon cancer. They searched Medline, Scopus, Cochrane, and the National Guideline Clearinghouse databases from Jan. 1, 1990 through June 30, 2006 for studies that offered survival data as a function of number of lymph nodes evaluated. These studies were evaluated for methodologic quality, design, and data source. The studies included a total of 61,371 patients. The authors found that 17 studies from nine countries were eligible for systematic review, including two secondary analyses of multicenter randomized trials of adjuvant chemotherapy for colon cancer, five population-based observational studies, and 10 single-institution retrospective cohort studies. Despite heterogeneity in methodology and differences in threshold numbers of lymph nodes evaluated (range, six to 40 lymph nodes), 16 of 17 studies reported that increased survival of patients with stage II colon cancer was associated with increased numbers of lymph nodes evaluated. Four of six studies with data from stage III patients also reported a positive association with survival among patients with stage III colon cancer. The authors concluded that the number of lymph nodes evaluated after surgical resection was positively associated with survival for patients with stage II and stage III colon cancer. These results support considering the number of lymph nodes evaluated as a measure of the quality of colon cancer care.

Chang GJ, Rodriguez-Bigas MA, Skibber JM, et al. Lymph node evaluation and survival after curative resection of colon cancer: systematic review. J Natl Cancer Inst. 2007;99:433-441.

Reprints: Dr. George J. Chang, Dept. of Surgical Oncology, University of Texas M.D. Anderson Cancer Center, 1400 Holcombe Blvd., Unit 444, Houston, TX 77030;

bullet Positive-block ratio in radical prostatectomy specimens as a predictor of PSA recurrence

Tumor volume has been an important variable in determining the probability of prostate-specific antigen recurrence in prostatic adenocarcinoma. Many studies have tried to determine an appropriate method of calculating tumor volume, but no single methodology has been agreed upon. The authors tested the hypothesis that the ratio of tumor-positive tissue blocks to total number of blocks submitted (positive-block ratio) can be used as an independent prognostic indicator for prostate-specific antigen (PSA) recurrence. They analyzed 504 patients who underwent total radical retropubic prostatectomy between 1990 and 1998, none of whom had preoperative radiation or androgen-deprivation therapy. The authors also reviewed clinical records. The mean positive-block ratio was 0.44 (median, 0.43; range, 0.05-1.0). The positive-block ratio was significantly associated with Gleason score, pathologic stage, surgical margin status, extraprostatic extension, seminal vesicle invasion, lymph node metastasis, perineural invasion, and preoperative serum PSA level (all, P<0.001). Using a multivariate Cox regression model, controlling for pathologic stage, Gleason score, lymph node metastasis, and surgical margin status, positive-block ratio was an independent predictor of PSA recurrence (hazard ratio, 2.3; 95% confidence interval, 1.06-4.83; P=0.03). Five-year PSA recurrence-free survival was 67 percent for those patients with a positive-block ratio of 0.43 or less and 42 percent for those with a positive-block ratio of more than 0.43 (P<0.001). The authors concluded that positive-block ratio is an independent predictor of PSA recurrence. This simple method of tumor measurement seems to be promising for quantifying tumor volume if the authors' findings are validated by subsequent reports.

Marks RA, Lin H, Koch MO, et al. Positive-block ratio in radical prostatectomy specimens is an independent predictor of prostate-specific antigen recurrence. Am J Surg Pathol. 2007;31:877-881.

Reprints: Dr. Liang Cheng, Indiana University School of Medicine, Clarian Pathology Laboratory, Room 4010, 350 W. 11th St., Indianapolis, IN 46202;

bullet Mucin profiles in signet-ring cell carcinoma

Signet-ring cell carcinoma is a poorly differentiated mucin-producing adenocarcinoma that may arise from many different organs, but all SRCCs share identical morphology. It is not possible to differentiate sites of origin for metastatic SRCC based on morphology alone. Mucins are high-molecular-weight glycoproteins differentially expressed in glandular epithelia and adenocarcinomas. The authors conducted a study to identify mucin profiles of primary and metastatic SRCCs using immunohistochemistry to determine whether mucin staining could help distinguish sites of origin. They retrieved from archival files 47 SRCCs, including 38 primary (21 stomach, 11 colorectum, and six breast) and nine metastases from these primary sites. Consecutive tissue sections were immunostained with monoclonal antibodies against MUC1, MUC2, MUC4, MUC5AC (MUC5), and MUC6 on separate slides. Cytoplasmic staining was scored based on proportion of positive tumor cells as 0+ (less than 5%), 1+ (5%-25%), 2+ (26%-50%), and 3+ (more than 50%). Mucin profiles were recorded as MUC+, MUCv, and MUC- for consistent, variable, and negative expression, respectively. The authors concluded that signet-ring cell carcinomas of the stomach, colorectum, and breast have distinct mucin expression patterns that are maintained in metastases. Mucin profiling may be useful for identifying the origin of a metastatic SRCC of unknown primary.

Nguyen MD, Plasil B, Wen P, et al. Mucin profiles in signet-ring cell carcinoma. Arch Pathol Lab Med. 2006;130:799-804.

Reprints: Dr. Wendy L. Frankel, Ohio State University, Dept. of Pathology, 401 E. Doan Hall, 410 W. 10th Ave., Columbus, OH 43210;

bullet Extranodal marginal zone B-cell lymphomas of the ocular adnexa

Extranodal marginal zone B-cell lymphomas of MALT type (MALT lymphomas) show site-dependent variations in their morphologic, phenotypic, and/or cytogenetic findings. The authors conducted a comprehensive analysis of 34 ocular adnexa MALT lymphomas, including interphase fluorescence in situ hybridization for MALT lymphoma-associated cytogenetic abnormalities and polymerase chain reaction for Chlamydia psittaci. The latter recently has been suggested to be associated with ocular adnexa lymphomas. A typical morphologic pattern was identified in 79 percent of cases, while overtly monocytoid cytology (12%), predominantly plasmacytic features (9%), and lymphoepithelial lesions (3%) were uncommon. Aberrant CD43 or CD5 expression was also uncommon (12% and 3%, respectively). Plasmacytic differentiation was associated with stage IV disease (P=0.036) and gains of chromosomes 3 or 18q (P=0.021), or both. A +3 was more frequent in the orbit than in the lacrimal gland or conjunctiva (P=0.005). Each of 31 cases was negative for MALT1 translocations. IGH gene translocations were identified in three cases (10%), although the translocation partner gene could not be identified. Polymerase chain-reaction assays targeting species-specific regions within the C. psittaci omp1 and omp2 genes were negative in 30 cases. The study identified the characteristic morphologic, phenotypic, and cytogenetic findings in ocular adnexa MALT lymphoma, including a subset differing from those arising at other anatomic sites. The frequent presence of +3 or +18q, or both, suggests that these abnormalities may contribute to lymphomagenesis. The authors concluded that the lack of C. psittaci in this series, in contrast to some prior reports, indicates that there may also be geographic heterogeneity in the pathogenesis of ocular adnexa MALT lymphoma.

Ruiz A, Reischl U, Swerdlow SH, et al. Extranodal marginal zone B-cell lymphomas of the ocular adnexa: multiparameter analysis of 34 cases including interphase molecular cytogenetics and PCR for Chlamydia psittaci. Am J Surg Pathol. 2007;31:792-802.

Reprints: Dr. James Cook, Dept. of Clinical Pathology, Cleveland Clinic, 9500 Euclid Ave., Cleveland, OH 44195

bullet Immunohistochemical analysis of langerin in LCH and pulmonary inflammatory and infectious diseases

Pulmonary Langerhans cell histiocytosis is an idiopathic condition that predominantly affects adult smokers. It is characterized by a nodular, interstitial proliferation of Langerhans cells around the distal airways with associated eosinophils, lymphocytes, and macrophages. Associated findings, such as fibrosis, emphysematous change, and bronchiolitis, can be reminiscent of other interstitial lung diseases. The markers CD1a and S100 traditionally have been used to distinguish pulmonary Langerhans cell histiocytosis (LCH) from other processes. However, little is known about the expression of langerin, a Langerhans cell-specific lectin, in pulmonary diseases. The authors examined the expression patterns of S100, CD1a, and langerin in LCH and other interstitial, inflammatory, and infectious processes in cases retrieved from files in the department of pathology at Brigham and Women's Hospital, Boston. Immunoreactivity was scored according to the number of cells staining per high-power field (400x) in areas of highest density averaged over four fields. Cases diagnosed as LCH based on histomorphology and positive CD1a and S100 staining demonstrated strong langerin positivity in lesional tissue. All cases of LCH contained more than 30 langerin and CD1a-positive cells per high-power field, with a mean of more than 100 cells per high-power field in lesional tissue. Of the other interstitial processes examined, only usual interstitial pneumonia demonstrated an increased number of Langerhans cells within epithelium and interstitium (mean, 14 cells per high-power field) as compared with normal lung (mean, six cells per high-power field). The authors concluded that langerin and CD1a serve as diagnostic markers in distinguishing LCH from other interstitial and inflammatory processes.

Sholl LM, Hornick JL, Pinkus JL, et al. Immunohistochemical analysis of langerin in Langerhans cell histiocytosis and pulmonary inflammatory and infectious diseases. Am J Surg Pathol. 2007;31:947-952.

Reprints: Dr. Robert F. Padera, Dept. of Pathology, Brigham and Women's Hospital, 75 Francis St., Boston, MA 02115;

Dr. Cibull is professor of pathology and laboratory medicine and direct of surgical pathology, University of Kentucky Medical Center, Lexington. Dr. Kesler is hematopathology fellow, University of Texas Southwestern Medical Center at Dallas.