Anatomic Abstracts

June 2005

Editors:
Michael Cibull, MD
Subodh Lele, MD
Melissa Kesler, MD

A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer
Consumption of the epidermis and the diagnosis of melanoma and Spitz nevus
KSHV-positive solid lymphomas: an extra-cavitary variant of primary effusion lymphoma

A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer

The likelihood of distant recurrence in patients with breast cancer who have no involved lymph nodes and estrogen-receptor-positive tumors is poorly defined by clinical and histo pathological measures. The authors tested whether the results of a reverse transcriptase-polymerase chain reaction (RT-PCR) assay of 21 prospectively selected genes in paraffin-embedded tumor tissue would correlate with the likelihood of distant recurrence in patients with node-negative, tamoxifen-treated breast cancer who were enrolled in the National Surgical Adjuvant Breast and Bowel Project clinical trial B-14. The levels of expression of 16 cancer-related genes and five reference genes were used in a prospectively defined algorithm to calculate a recurrence score and to determine a risk group (low, intermediate, or high) for each patient. Adequate RT-PCR profiles were obtained in 668 of 675 tumor blocks. The proportion of patients categorized as having a low, intermediate, or high risk by the RT-PCR assay was 51, 22, and 27 percent, respectively. The Kaplan-Meier estimates of the rates of distant recurrence at 10 years in the low-risk, intermediate-risk, and high-risk groups were 6.8 percent (95 percent confidence interval, 4.0 to 9.6), 14.3 percent (95 percent confidence interval, 8.3 to 20.3), and 30.5 percent (95 percent confidence interval, 23.6 to 37.4). The rate in the low-risk group was significantly lower than that in the high-risk group (P<0.001). In a multivariate Cox model, the recurrence score was also predictive of overall survival (P<0.001) and could be used as a continuous function to predict distant recurrence in individual patients. The authors concluded that the recurrence score has been validated as quantifying the likelihood of distant recurrence in tamoxifen-treated patients with node-negative, estrogen-receptor-positive breast cancer.

Paik S, Shak S, Tang G, et al. A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med. 2004;351:2817–2826.

Reprints: S. Paik, National Surgical Adjuvant Breast and Bowel Project, East Commons Professional Building, 4 Allegheny Center, fifth floor, Pittsburgh, PA 15212-5234; spaik.nejm@nsabp.org

Consumption of the epidermis and the diagnosis of melanoma and Spitz nevus

The distinction between melanoma and its most important simulant, Spitz nevus, is usually made microscopically. The authors consider consumption of the epidermis (COE) to be an additional diagnostic criterion. They define COE as thinning of the epidermis with attenuation of the basal and suprabasal layers and loss of rete ridges in areas of direct contact with neoplastic melanocytes. The authors analyzed 102 unequivocal melanomas and 125 unequivocal Spitz nevi for the presence of COE. COE had not been used in the diagnosis of these cases because the authors were unaware of the criterion at the time the cases were first evaluated. COE was found in 88 of 102 (86 percent) melanomas but only 12 of 125 (9.6 percent) Spitz nevi (P<0.001). The authors then looked for COE in an independent set of 61 ambiguous melanocytic lesions with overlapping histopathologic features that could not be classified unequivocally as Spitz nevus or melanoma. The cases were analyzed by comparative genomic hybridization (CGH) for aberration patterns suggesting a benign or malignant process based on previous studies. COE was found in only six of 42 (14 percent) of the ambiguous cases in which CGH suggested a benign process and 14 of 19 (74 percent) of the ambiguous cases in which CGH suggested melanoma (P<0.001). This data suggested that COE is a useful criterion for evaluating melanocytic neoplasms. Because COE was frequently found at the edges of ulcers in the majority of ulcerated melanomas, the thinning of the epidermis in COE may represent an early phase of ulceration. This may prove to be important in distinguishing ulceration due to an effect of the tumor from ulceration due to trauma, which would be expected not to have the same prognostic import. Additional studies are required to analyze the prognostic value of COE.

Hantschke M, Bastian BC, LeBoit PE. Consumption of the epidermis: a diagnostic criterion for the differential diagnosis of melanoma and Spitz nevus. Am J Surg Pathol. 2004;28:1621–1625.

Reprints: Dr. Philip E. LeBoit, Dermatopathology Section, Departments of Pathology and Dermatology, University of California, San Francisco, 1701 Divisadero St., Suite 350, San Francisco, CA 94115; philip1@itsa.ucsf.edu

KSHV-positive solid lymphomas: an extra-cavitary variant of primary effusion lymphoma

Primary effusion lymphoma is a unique type of non-Hodgkin lymphoma associated with Kaposi’s sarcoma-associated herpesvirus (KSHV; HHV-8). Primary effusion lymphomas (PELs) occur exclusively as lymphomatous effusions and exhibit a distinct constellation of clinical, morphologic, immunophenotypic, and molecular characteristics. Rare HHV-8-positive immunoblastic lymphomas have been described in solid tissue, but whether these represent part of the spectrum of PEL has not been determined. The authors compared the morphologic, immunophenotypic, and molecular features of HHV-8-positive solid lymphomas occurring in eight HIV+/AIDS patients with 29 PELs. They found that the HHV-8-positive solid lymphomas were indistinguishable from the PELs with regard to morphology (immunoblastic/anaplastic), immunophenotype (CD45, CD30, EMA, and CD138 were positive; CD10, bcl-6, CD15, and T-cell antigens were negative), and genotype (100 percent immunoglobulin genes rearranged; no identifiable abnormalities in c-myc, bcl-6, bcl-1, or bcl-2; EBV positive). The only identifiable phenotypic difference was that the HHV-8-positive solid lymphomas appeared to express B cell-associated antigens (CD79a, CD20) and cytoplasmic or surface immunoglobulin, or both, slightly more frequently than the PELs (25 percent each in solid lymphomas versus less than five percent and 15 percent, respectively, in PEL; P=0.11 and P=0.08, respectively). The clinical presentation, except for lack of effusion, and course were also similar. The authors concluded that their findings strongly suggest that HHV-8-positive solid lymphomas are part of the spectrum of PEL, and they propose that such lymphomas be designated as extra-cavitary PELs.

Chadburn A, Hyjek E, Mathew S, et al. KSHV-positive solid lymphomas represent an extra-cavitary variant of primary effusion lymphoma. Am J Surg Pathol. 2004;28: 1401–1416.

Reprints: Dr. Amy Chadburn, Dept. of Pathology and Laboratory Medicine, Weill Medical College of Cornell University, 525 E. 68th St., New York, NY 10021; achadbur@mail.med.cornell.edu