Anatomic Abstracts

February 2008

Editor:
Michael Cibull, MD
Melissa Kesler, MD

Plasmablastic cytomorphologic features in plasma cell neoplasms in immunocompetent patients
Distinguishing between mitotically active cellular fibroma and fibrosarcoma
Role of advanced reagents in improving immunohistochemistry

Plasmablastic cytomorphologic features in plasma cell neoplasms in immunocompetent patients

Multiple myeloma is rarely associated with Epstein-Barr virus, irrespective of HIV status, in contrast with its morphologic mimic, plasmablastic lymphoma. The latter occurs primarily in immunocompromised patients with frequent Epstein-Barr virus (EBV) association. The authors conducted a study of the association between EBV and multiple myeloma in which they assessed 58 consecutive immunocompetent patients. The authors found plasmablastic cytomorphologic features in two of four patients with plasmacytomas and 14 (26%) of 54 with multiple myeloma. Four of the tumors (one plasmacytoma and three multiple myelomas) were EBV-encoded RNA (EBER)-positive, with plasmablastic cytomorphologic features in three. The patient with plasmacytoma was disease free for 75 months, and the remaining three patients with multiple myeloma died at 15, 74, and 97 months, respectively. The median survival rate for patients with EBER-multiple myeloma was 12 months. EBV+ tumors were associated with plasmablastic cytomorphologic features and high labeling indices. Rare EBER+ plasmablastic plasma cell tumors exist in immunocompetent patients. These tumors may have been driven by EBV to gain the plasmablastic cytomorphologic features and high proliferation fraction. A large cohort study is needed to clarify the prognostic impact of EBV on immunocompetent patients with multiple myeloma.

Chang ST, Liao YL, Lu CL, et al. Plasmablastic cytomorphologic features in plasma cell neoplasms in immunocompetent patients are significantly associated with EBV. Am J Clin Pathol. 2007; 128 (2): 339– 344.

Reprints: Dr. S. S. Chuang, Dept. of Pathology, Chi-Mei Medical Center, 901 Chung-Hwa Rd., Yung-Kang City, Tainan County 710, Taiwan

Distinguishing between mitotically active cellular fibroma and fibrosarcoma

Cellular fibroblastic tumors of the ovary are classified as cellular fibroma or fibrosarcoma. The former are characterized by bland nuclei, three or fewer mitotic figures per 10 high-power fields (MFs/10 HPFs), and low malignant potential. Fibrosarcomas, on the other hand, usually have severe nuclear atypia, four or more MFs/10 HPFs, and an aggressive clinical course. The authors investigated the prognosis of cellular fibromatous tumors with four or more MFs/10 HPFs and low-grade cytology, which is not established. It has been their anecdotal experience that otherwise typical cellular fibromas with four or more MFs/10 HPFs usually have a benign clinical course, suggesting that such tumors should be regarded as mitotically active cellular fibroma (MACF) rather than fibrosarcoma. The authors analyzed 75 cellular fibromatous neoplasms to determine their clinicopathologic features and the appropriateness of MACF as a designation for otherwise typical cellular fibromas with four or more MFs/10 HPFs. The mean age of patients with cellular fibroma (n=35; zero to three MFs/10 HPFs) and MACF (n=40; four or more MFs/10 HPFs) was 51 and 41 years, respectively. Patients most commonly presented with symptoms related to a pelvic mass. All tumors were unilateral. The mean tumor size was 8.0 cm for cellular fibromas and 9.4 cm for MACFs. The majority of the tumors were solid, and approximately one-third of them had a cystic component. Ovarian surface adhesions, involvement of the ovarian surface, or both, was present in six percent of cellular fibromas and 10 percent of MACFs. Eleven percent of cellular fibromas and 13 percent of MACFs were associated with extraovarian involvement. All tumors consisted of cellular, intersecting bundles of spindle cells with bland nuclear features. The mean highest mitotic count for MACFs was 6.7 MFs/10 HPFs (range, four to 19 MFs/10 HPFs). Followup of three months to 12 years (mean, 4.75 years) was available in 18 of the 40 patients with MACFs and was uneventful in all cases. The authors concluded that cellular fibromatous neoplasms with bland cytology and elevated mitotic counts are associated with favorable patient outcome and should be diagnosed as MACF rather than fibrosarcoma, which usually has moderate to severe atypia and elevated mitotic rates. Long-term followup of patients with cellular fibromas and MACFs is appropriate since prior observations have shown that even typical cellular fibromas can occasionally recur locally, particularly if they are associated with rupture or adherence.

Irving JA, Alkushi A, Young RH, et al. Cellular fibromas of the ovary: a study of 75 cases including 40 mitotically active tumors emphasizing their distinction from fibrosarcoma. Am J Surg Pathol. 2006;30:929–938.

Reprints: Dr. Julie A. Irving, Dept. of Pathology, 855 W. 12th Ave., 1st floor JPPN, Vancouver General Hospital, Vancouver, British Columbia, Canada V5Z 1M9; julie.irving@vch.ca

Role of advanced reagents in improving immunohistochemistry

Incorrect results in immunohistochemistry are frequently caused by nonstandardized antigen retrieval protocols and fluids, poor quality antibodies, and endogenous biotin. The recent development of advanced reagents, including bifunctional SkipDewax pretreatment solution (BSPS), rabbit monoclonal antibodies, and biotin-free polymer detection systems, may resolve these problems. The authors conducted a study to determine whether BSPS, rabbit monoclonal antibodies, and biotin-free polymer detection systems improve the accuracy of immunohistochemistry. The intent of the study was also to optimize a new protocol consisting of a combination of BSPS, rabbit monoclonal antibodies, and polymer detection systems, and to compare it with a conventional protocol. The efficacies of BSPS, rabbit monoclonal antibodies, and polymer detection systems were compared with those of their respective conventional reagents using multi-tissue spring-roll sections. The new protocol was compared with a conventional protocol using Ki-67 immunostaining of 49 colorectal carcinoma specimens. The authors found that for antigen retrieval, BSPS resulted in similar or better tissue staining than an EDTA solution, but the efficacy of BSPS decreased when it was reused. Most rabbit monoclonal antibodies resulted in a greater proportion of positive cells than the corresponding non-rabbit monoclonal antibodies, which did not produce satisfactory results in the absence of antigen retrieval. The polymer detection systems Bond, ChemMate, and SuperPicture resulted in a high percentage of positive cells, good staining intensities, and low backgrounds. Other polymer detection systems, except that from Ventana, resulted in high backgrounds and false positivity. The new combined protocol resulted in better Ki-67 staining than the conventional assay. The authors concluded that bifunctional SkipDewax pretreatment solution, rabbit monoclonal antibodies, and polymer detection systems improve staining quality and the diagnostic accuracy of immunohistochemistry assays and provide a foundation for standardization.

Wong SC, Chan JK, Lo ES, et al. The contribution of bifunctional SkipDewax pretreatment solution, rabbit monoclonal antibodies, and polymer detection systems in immunohistochemistry. Arch Pathol Lab Med. 2007;131:1047–1055.

Reprints: Dr. S.C. Cesar Wong, Dept. of Clinical Oncology, Sir Y.K. Pao Centre for Cancer, Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China; cesar01@netvigator.com.