College of American Pathologists
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  Anatomic Abstracts






June 2007

Michael Cibull, MD
Melissa Kesler, MD

DLBCLs presenting with an associated low-grade component at diagnosis
Changes in breast cancer management resulting from case review at a tumor board
Occult tumor cells in lymph nodes from patients with colorectal carcinoma
Significance of Epstein-Barr virus in nodal peripheral T-cell lymphoma, unspecified Predicting sentinel node status in AJCC stage I/II primary cutaneous melanoma

bullet DLBCLs presenting with an associated low-grade component at diagnosis

Some diffuse large B-cell lymphomas present at diagnosis with associated morphologic features of small B-cell non-Hodgkin lymphoma and may arise from the transformation of a previously unknown indolent low-grade lymphoma. The characteristics and outcome of these particular diffuse large B-cell lymphomas (DLBCLs) are not well known. The authors reviewed DLBCL patients diagnosed over 12 years in their hematology department and retrieved 60 DLBCLs that could have occurred from the transformation of marginal zone B-cell non-Hodgkin lymphoma (32 patients), follicular NHL (22 patients), and small lymphocytic NHL (six patients). They compared them to 180 matched patients with de novo DLBCL. Patients were a median age of 55 years and presented with poor performance status (33 percent), disseminated disease (97 percent), more than one extranodal site (50 percent), and increased lactate dehydrogenase level (55 percent). Complete remission with multi-drug chemotherapy regimens was achieved in 60 percent of the patients, but 48 percent relapsed: 28 percent with aggressive and 20 percent with indolent histology, respectively. Overall survival and freedom-from-progression rates at five years were 57 percent and 33 percent, respectively. The matched-control analysis showed that patients with transformed NHL at diagnosis had lower complete response to chemotherapy (P=0.004) and a higher progression rate (P=0.03); no difference was observed in overall survival (P=0.21). The authors concluded that, compared to de novo DLBCL, transformed NHL at diagnosis has a similar overall survival rate but lower complete response to initial treatment and a higher risk of indolent relapses.

Ghesquieres H, Berger F, Felman P, et al. Clinicopathologic characteristics and outcome of diffuse large B-cell lymphomas presenting with an associated low-grade component at diagnosis. J Clin Oncol. 2006;24(33):5234–5241.

Reprints: Dr. Gilles Salles, Service d’Hématologie, Centre Hospitalier Lyon-Sud, 69495 Pierre-Bénite, France;

bullet Changes in breast cancer management resulting from case review at a tumor board

The treatment of breast cancer requires a multidisciplinary approach, and patients are often referred to a multidisciplinary cancer clinic. The authors evaluated the impact of this approach on the surgical management of breast cancer. They retrospectively reviewed the medical records of 149 consecutive patients referred to a multidisciplinary breast cancer clinic over a one-year period with a diagnosis of breast cancer for alterations in radiologic, pathologic, surgical, and medical interpretations and the effect these alterations had on recommendations for surgical management. A review of the imaging studies resulted in changes in interpretations in 67 of the 149 patients studied (45%). This resulted in a change in surgical management in 11 percent of patients. Review of the pathology resulted in changes in interpretation for 43 of the 149 patients (29%). Thirteen patients (9%) had surgical management changes made solely as a result of pathologic reinterpretation. In 51 patients (34%), a change in surgical management was recommended after discussion with the surgeons, medical oncologists, and radiation oncologists that was not based on reinterpreting the radiologic or pathologic findings. Overall, a second evaluation of patients referred to a multidisciplinary tumor board led to changes in the recommendations for surgical management in 77 of 149 of the patients studied (52%). The authors concluded that changes in management stemmed from differences in mammographic interpretation, pathologic interpretation, and evaluation by medical and radiation oncologists and surgical breast specialists. Multidisciplinary review can provide patients with useful additional information when making difficult treatment decisions.

Newman EA, Guest AB, Helvie MA, et al. Changes in surgical management resulting from case review at a breast cancer multidisciplinary tumor board. Cancer. 2006;107:2346–2351.

Reprints: Dr. Michael S. Sabel, Dept. of Surgery, University of Michigan Comprehensive Cancer Center, 3304 Cancer Center, 1500 E. Medical Center Drive, Ann Arbor, MI 48109;

bullet Occult tumor cells in lymph nodes from patients with colorectal carcinoma

Approximately 30 percent of patients with lymph node-negative colorectal carcinoma die of tumor recurrence, which can be related to the presence of tumor cells in lymph nodes that are not detected by conventional histopathologic analysis. However, the prognostic significance of occult cancer cells is uncertain. The authors evaluated the incidence and prognostic significance of occult cancer cells in lymph nodes from 395 consecutive patients with curatively resected stage IIA colorectal carcinoma using immunohistochemistry for cytokeratin 20. Immunostained tumor cells were categorized as micrometastases (MCMs) or isolated tumor cells (ITCs) according to the American Joint Committee on Cancer criteria. The detection rates were compared with the clinicopathologic characteristics of the patients and with cancer-specific survival rates. The median followup was 128 months. Micrometastases were detected in 39 patients (9.9%) and ITCs were found in 112 (28.4%), for an overall frequency of 38.2 percent. None of the clinicopathologic parameters examined was correlated with the presence of occult cancer cells. Patients with ITCs and those with negative lymph nodes showed a similar survival rate (77.7% and 78.3%, respectively), whereas patients with MCMs had a lower survival rate (64.1%). At univariate analysis, MCMs, tumor growth pattern, extent of tumor spread, and Crohn’s-like lymphoid reaction influenced survival rates significantly. Nevertheless, at multivariate analysis, only pattern of tumor growth and extent of tumor spread were independent prognostic factors. The authors concluded that immunostained tumor cells are detected relatively frequently in the lymph nodes of patients with stage IIA colorectal cancer, but they have no significant effect on prognosis.

Messerini L, Cianchi F, Cortesini C, et al. Incidence and prognostic significance of occult tumor cells in lymph nodes from patients with stage IIA colorectal carcinoma. Hum Pathol. 2006;27:1259–1267.

Reprints: L. Messerini, Dipartimento di Patologia Umana ed Oncologia, Università degli Studi di Firenze, 50134 Firenze, Italy;

bullet Significance of Epstein-Barr virus in nodal peripheral T-cell lymphoma, unspecified

Peripheral T-cell lymphomas are rare, and patients have a dismal prognosis. The most frequent subtype is peripheral T-cell lymphoma (PTCL), unspecified. Epstein-Barr virus (EBV) has been detected in about 40 percent of cases, but its prognostic significance is not fully established. The authors of this study analyzed lymph node samples from 110 patients with PTCL, unspecified included in LNH87 and LNH93 trials. EBV status was studied by EBV-encoded small RNA in situ hybridization (EBER-ISH). EBER-ISH showed positive cells in 45 (41%) of 110 patients. Pretreatment characteristics were comparable between positive and negative cases, except for male gender (80% versus 60%, respectively; P=0.02). Only half of patients achieved complete remission, with a five-year event-free survival (EFS) and overall survival rate of 21 and 30 percent, respectively. EBER-ISH positivity was the sole factor linked with worse EFS, with a five-year probability of 11 percent for positive patients. In univariate analysis, factors affecting overall survival were EBER-ISH positivity, high LDH level, and age older than 60 years. In multivariate analysis, EBER-ISH was associated with a worse overall survival rate in the elderly population. Time-dependent analysis showed that the negative impact of EBV was seen in the first two years after diagnosis. The authors concluded that these results warrant further studies regarding pathogenesis and specific treatment approaches for EBV-associated PTCL patients.

Dupuis J, Emile JF, Mounier N, et al. Prognostic significance of Epstein-Barr virus in nodal peri­pheral T-cell lymphoma, unspecified: a Groupe d’Etude des Lymphomes de l’Adulte (GELA) study. Blood. 2006;108(13):4163–4169.

Correspondence: Philippe Gaulard, Département de Pathologie, Inserm U617, CHU Henri Mondor, AP-HP, 94010-Créteil, France;

bullet Predicting sentinel node status in AJCC stage I/II primary cutaneous melanoma

Sentinel lymph node status is an important prognostic factor for survival for patients with primary cutaneous melanoma. To address the issue of selecting patients at high and low risk for a positive sentinel lymph node (SLN), the authors of this study sought prognostic factors that predict SLN involvement by examining characteristics of the primary tumor and the patient within the context of a biological model of melanoma progression. The authors studied 682 patients with primary vertical growth phase melanoma and no clinical evidence of metastatic disease who underwent SLN biopsy between 1995 and 2003. They used logistic regression and classification tree analyses to investigate the association between SLN positivity and Breslow thickness, Clark level, tumor infiltrating lymphocytes (TIL), ulceration, mitotic rate, lesion site, gender, and age. In all, 88 of the 682 patients had one or more positive SLNs (12.9%). In a multivariate analysis, mitotic rate, TIL, and thickness were found to be independent prognostic factors for SLN positivity. In the classification tree, four risk groups were defined, ranging from minimal risk (2.1%) to high risk (40.4%). In lesions of 2.0 mm or less, mitotic rate was important in risk-stratifying patients; in lesions greater than 2.0 mm, TIL was important. By incorporating biologically base variables such as vertical growth phase, TIL, and mitotic rate with thickness into a prognostic model, patients at high risk and minimal risk for SLN positivity can be identified. If validated, this model can be used in patient management and trial design to select patients who should undergo or be spared SLN biopsy.

Kruper LL, Spitz FR, Czerniecki BJ, et al. Predicting sentinel node status in AJCC stage I/II primary cutaneous melanoma. Cancer. 2006;107:2436–2445.

Reprints: Dr. Laura L. Kruper, Dept. of Surgery, Hospital of the University of Pennsylvania, Maloney Building, 4th Floor, 3400 Spruce St., Philadelphia, PA 19104;

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.