College of American Pathologists
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  Anatomic Abstracts






January 2008

Michael Cibull, MD
Melissa Kesler, MD

Prognostic impact of germinal center phenotype in DLBCL patients treated with immunochemotherapy
Treatment of micropapillary bladder cancer: a retrospective review
Fuhrman grading is not appropriate for chromophobe renal cell carcinoma
Epidermal growth factor receptor and gastrointestinal stromal tumor

Prognostic impact of germinal center phenotype Prognostic impact of germinal center phenotype in
    DLBCL patients treated with immunochemotherapy

Germinal center and non-germinal center phenotypes predict outcome in diffuse large B–cell lymphoma (DLBCL) and can be used to stratify chemotherapy–treated patients into low- and high-risk groups. To determine how a combination of rituximab and chemotherapy influences germinal center-associated clinical outcome, the authors identified GC and non–GC phenotypes immunohistochemically (based on CD10, bcl–6, and MUM–1 staining patterns) from samples of 90 de novo DLBCL patients treated with rituximab in combination with a CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone)–like regimen (immunochemotherapy). A group of 104 patients previously treated with chemotherapy served as controls. Consistent with previous studies, chemotherapy-treated patients with immunohistochemically defined GC phenotype displayed significantly better overall and failure-free survival rates than did those in the non–GC group (overall survival, 70% versus 47%, P=0.012; failure–free survival, 59% versus 30%, P=0.001). In contrast, an immunohistochemically defined GC phenotype did not predict outcome in immunochemotherapy–treated patients (overall survival, 77% versus 76%, P=ns; failure-free survival, 68% versus 63%, P=ns). In comparison, the International Prognostic Index (IPI) could separate high–risk patients from low– and intermediate–risk groups (overall survival, 84% versus 63%, P=0.030; failure–free survival, 79% versus 52%, P=0.028). The authors concluded that rituximab combined with chemotherapy seems to eliminate the prognostic value of immunohistochemically defined GC and non-GC phenotypes in DLBCL.

Nyman H, Adde M, Karjalainen–Lindsberg ML, et al. Prognostic impact of immunohistochemically defined germinal center phenotype in diffuse large B–cell lymphoma patients treated with immunochemotherapy. Blood. 2007;109:4930–4935.

Correspondence: Sirpa Leppä, Dept. of Oncology, Helsinki University Central Hospital, P.O. Box 180, FIN-00029, Helsinki, Finland

Treatment of micropapillary bladder cancer Treatment of micropapillary bladder cancer: a retrospective review

The authors performed a retrospective review of their experience with micropapillary bladder carcinoma, a rare variant of urothelial carcinoma, to improve their understanding of the disease. They reviewed the records of 100 consecutive patients with micropapillary bladder cancer who were evaluated at the University of Texas M. D. Anderson Cancer Center. The patients were a mean age of 64.7 years and the male:female ratio was 10:1. The tumor-node-metastasis stage of disease at presentation was Ta in five patients, carcinoma in situ (CIS) in four patients, T1 in 35 patients, T2 in 26 patients, T3 in seven patients, T4 in six patients, N+ in nine patients, and M+ in eight patients. Kaplan-Meier estimates of five- and 10-year overall survival rates were 51 percent and 24 percent, respectively. Bladder-sparing therapy with intravesical bacillus Calmette-Guerin therapy was attempted in 27 of 44 patients with nonmuscle-invasive disease, and 67 percent (18 patients) developed disease progression (cT2 or greater), including 22 percent (six patients) who developed metastatic disease. Of 55 patients undergoing radical cystectomy for surgically resectable disease (cT4a or less), 23 received neoadjuvant chemotherapy and 32 were treated with initial cystectomy, with no significant difference noted in stage distribution between the two groups. For the 23 patients treated with neoadjuvant chemotherapy, the median overall survival rate was 43.2 months, with 32 percent of the patients still alive at five years. For the 32 patients treated with initial cystectomy, the median survival rate had not been reached at the time of last followup, with 71 percent still alive at five years. The authors concluded that micropapillary bladder cancer is associated with a poor prognosis. Intravesical therapy appears to be ineffective for this disease, and patients with surgically resectable disease should be offered early radical cystectomy.

Kamat AM, Dinney CP, Gee JR, et al. Micropapillary bladder cancer: a review of the University of Texas M. D. Anderson Cancer Center experience with 100 consecutive patients. Cancer. 2007;110:62–67.

Reprints: Dr. Ashish M. Kamat, Dept. of Urology, Unit 1373, University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030;

Fuhrman grading is not appropriate Fuhrman grading is not appropriate for
    chromophobe renal cell carcinoma

The authors conducted a study to assess the prognostic effectiveness of Fuhrman nuclear grading and the components of this grading system in a series of chromophobe renal cell carcinomas. They investigated 87 cases of chromophobe renal cell carcinoma involving 47 males and 40 females who were 28 to 78 years of age. The carcinomas ranged from 25 to 180 mm in size. On tumor-node-metastasis (TNM) staging, there were 38 stage I, 25 stage II, 22 stage III, and two stage IV tumors. Whole tumor Fuhrman grading was grade 1, six cases; grade 2, 72 cases; grade 3, eight cases; and grade 4, one case. Focal (single high-power field) grading was grade 1, one case; grade 2, 62 cases; grade 3, 21 cases; and grade 4, three cases. On assignment of nucleolar grading using Fuhrman criteria, there were 37 grade 1, 44 grade 2, and four grade 3 tumors on whole tumor assessment and three grade 1, 63 grade 2, and 21 grade 3 tumors on assessment of the high-power field showing the greatest degree of nuclear pleomorphism. Measurements of nuclear size showed nuclear area ranging from 26.14 to 100.74 µm2, nuclear perimeter from 19.73 to 39.28 µm, and nuclear major axis from 6.49 to 13.21 µm. The ranges of measures of nuclear shape were shape factor 0.798 to 0.890, compactness 14.260 to 15.843 m, and feret diameter 5.694 to 11.242. Followup ranged from one to 150 months, and eight patients died of tumor-related causes five to 53 months after diagnosis. On log rank testing against survival, only patient age (P=0.016) and tumor maximum diameter (P=0.0055) were significant—patient gender and TNM stage were not significant. Whole tumor and focal Fuhrman grading, as well as all measures of nucleolar prominence, nuclear size, and nuclear shape, showed no significant association with outcome. The authors concluded that neither Fuhrman grading nor any of the components of the Fuhrman grading system are useful as prognostic indicators for this tumor type.

Delahunt B, Sika-Paotonu D, Bethwaite PB, et al. Fuhrman grading is not appropriate for chromophobe renal cell carcinoma. Am J Surg Pathol. 2007;31:957–960.

Reprints: Brett Delahunt, Dept. of Pathology and Molecular Medicine, Wellington School of Medicine and Health Sciences, P.O. Box 7347, Wellington South, New Zealand;

Epidermal growth factor Epidermal growth factor receptor and gastrointestinal stromal tumor

Gastrointestinal stromal tumor is the most common mesenchymal neoplasm of the gastrointestinal tract. Mutually exclusive KIT or platelet-derived growth factor receptor mutations are key events in gastrointestinal stromal tumor pathogenesis, and specific treatment targeting KIT/platelet-derived growth factor receptor activation is available. Epidermal growth factor receptor (EGFR) plays an important role in cancer biology and constitutes a promising molecular target of therapy. The authors conducted a study to investigate EGFR immunohistochemical expression and EGFR gene amplification in 82 consecutive gastrointestinal stromal tumor cases using a tissue microarray technique. They reviewed hematoxylin-and-eosin-stained sections and clinical information and investigated the expression of CD117 (KIT), CD34, and EGFR by immunohistochemistry. They also determined EGFR gene copy number using fluorescence in situ hybridization (FISH). Immunohistochemistry revealed that CD117 and CD34 were expressed in 96 and 57 percent of tumors, respectively. Variable EGFR protein immunohistochemical overexpression was detected in 96 percent of gastrointestinal stromal tumor cases. However, none of the 75 cases with represented tumor tissue cores and countable fluorescence signals exhibited EGFR gene amplification by FISH. The study results showed that there is no correlation between EGFR protein overexpression by immunohistochemistry and EGFR gene amplification by FISH. The authors concluded that additional studies should be undertaken because the mechanisms of EGFR protein overexpression are not well understood and because anti-EGFR therapy may be beneficial for patients with gastrointestinal stromal tumor that overexpresses EGFR.

Lopes LF, Bacchi CE. EGFR and gastrointestinal stromal tumor: an immunohistochemical and FISH study of 82 cases. Mod Pathol. 2007;20:990–994

Reprints: Dr. C. E. Bacchi, Consultoria em Patologia, Rua Major Leonidas Cardoso, 739, Botucatu, Sao Paulo, 18602-010, Brazil;

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.