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  Anatomic Abstracts

 

 

 

May 2008

Editor:
Michael Cibull, MD
Melissa Kesler, MD

Significance of isolated HMB45 or Melan A-positive cells in melanoma SLN
Immunohistochemical heterogeneity of specific basal breast carcinomas
Malignancies in women with BRCA mutations undergoing surgery to reduce cancer risk
Distinguishing Burkitt lymphoma from diffuse large B-cell lymphoma
Immunostaining in atypical immature squamous metaplasia of uterine cervix

Significance of isolated HMB45 or Melan A-positive cells in melanoma SLN Significance of isolated HMB45 or Melan A-positive cells in melanoma SLN

Detection of micrometastases in the sentinel lymph node is an important prognostic tool in melanoma. The use of immunohistochemistry with melanocytic markers such an HMB45 and Melan A increases the detection rate for micrometastases, but cases with isolated immunohistochemically positive cells (IPC) exist. To determine the prognostic significance of isolated HMB45 or Melan A-positive cells, or both, in melanoma sentinel lymph node (SLN), the authors compared the clinical course of 47 patients with IPC to 308 patients with negative SLN and 122 patients with micrometastases. The mean followup was 38.1 months. By Kaplan-Meier analyses, relapse-free survival and overall survival of patients with IPC were similar to that for SLN-negative patients, whereas patients with micrometastases had a significantly worse relapse-free and overall survi­val rate. In the 47 patients with IPC, six relapses (12.8%) and three melanoma-related deaths (6.4%) occurred; in the SLN-negative patients, 36 relapses (11.7%) and 17 melanoma-related deaths (5.5%) occurred; and in the patients with micrometastases, 46 relapses (37.7%) and 29 melanoma-related deaths (23.8%) occurred. The prognosis for patients with IPC in SLN did not correlate with type of positive staining (HMB45, Melan A, or both), capsular involvement, number of cells, presence of cytologic atypias of IPC, or tumor penetrative depth. The authors concluded that with short-term followup, IPC in melanoma SLN are without prognostic significance.

Satzger I, Volker B, Meier A, et al. Prognostic significance of isolated HMB45 or Melan A positive cells in melanoma sentinel lymph nodes. Am J Surg Pathol. 2007; 31: 1175– 1180.

Reprints: Dr. Imke Satzger, Dept. of Dermatology and Allergology, Hannover Medical School, Ricklinger Str. 5, D-30449 Hannover, Germany; satzger.imke@mh-hannover.de
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Immunohistochemical heterogeneity of specific basal breast carcinomas Immunohistochemical heterogeneity of specific basal breast carcinomas

Basal breast carcinomas triple negative for estrogen receptors, progesterone receptors, and HER2/neu breast carcinomas are more aggressive than conventional neoplasms. The authors studied 64 cases with immunohistochemistry, using 23 anti­bodies, to characterize diverse pathological pathways. A basal cytokeratin was identified in 81 percent of tumors, and vimentin was identified in 55 percent. The mean Ki-67 index was 46 percent (range, 10 to 90%). Coincident expression of p50 and p65, which suggests an active nuclear factor-κβ factor, was present in 13 percent of neoplasms. Epithelial growth factor receptor (EGFR), insulin—like growth factor-1 receptor (IGF-1R), or c-kit (CD117) was identified in 77 percent of tumors. Loss of protein tyrosine phosphatase was found in 14 percent, and Akt activation was present in 28 percent. Several differences were identified between two subtypes of basal breast carcinomas. The pure variant (negative S-100 and actin) was more frequently associated with in situ carcinoma (P=0.019) and pBad overexpression (P=0.098). The myoepithelial variant (positive S-100 or actin) showed more frequent tumor necrosis (P=0.048), vimentin expression (P=0.0001), CD117 expression (P=0.001), and activated caspase-3 (P=0.089). IGF-1R could be as important as EGFR for the growth of these neoplasms. The authors concluded that basal cell carcinoma has at least two subtypes with distinct microscopic and immunohistochemical features.

Lerma E, Peiro G, Ramón T, et al. Immunohistochemical heterogeneity of breast carcinomas negative for estrogen receptors, progesterone receptors and HER2/neu (basal-like breast carcinomas). Mod Pathol. 2007: 20: 1200– 1207.

Reprints: Dr. E. Lerma, Dept. of Pathology, Hospital de la Santa Creu i Sant Pau, Avda. Sant Antonio Ma Claret, 167, Barcelona 08025, Spain; elerma@santpau.es
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Malignancies in women with BRCA mutations undergoing surgery to reduce cancer risk Malignancies in women with BRCA mutations undergoing surgery to reduce cancer risk

The authors conducted a study to review the frequency and location of malignancies detected after prophylactic salpingo-oophorectomy in women with BRCA mutations. They reviewed the medical records and pathology findings from BRCA-positive women who underwent complete examination of the adnexa and were undergoing prophylactic surgery to reduce their risk of developing ovarian cancer. The authors identified for the study 122 BRCA-positive women who underwent prophylactic surgery in the division of gynecologic oncology at Brigham and Women’s Hospital, Boston, between January 1999 and January 2007. The subjects were a median age of 46.5 years (range, 33 to 76 years). Seven (5.7%) were found to have an early malignancy in the upper genital tract, and all patients were age 44 years or older at diagnosis. Of seven consecutive cancers culled between January 1999 and January 2007, all originated in the fimbrial or ampullary region of the tube; six had an early (intraepithelial) component. Two were associated with surface implants on the ovary, and two required repeated sectioning to detect microscopic carcinomas in the fimbria. The authors concluded that the distal fallopian tube seems to be the dominant site of origin for early malignancies detected in approximately six percent of women undergoing ovarian cancer risk—reduction surgery. The greatest proportion of serous cancer risk in BRCA mutation-positive women should be assigned to the fimbria rather than the ovary. Future clinical and research protocols should thoroughly examine the fimbria, including multiple sections from each tissue block, to maximize early detection of malignancies in this population.

Callahan MJ, Crum CP, Medeiros F, et al. Primary fallopian tube malignancies in BRCA-positive women undergoing surgery for ovarian cancer risk reduction. J Clin Oncol. 2007;25:3985–3990.

Reprints: Dr. Michael G. Muto, Brigham and Women’s Hospital, 75 Francis St., Boston, MA 02115; mmuto@partners.org
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Distinguishing Burkitt lymphoma from diffuse large B-cell lymphoma Distinguishing Burkitt lymphoma from diffuse large B-cell lymphoma

Burkitt lymphoma is characterized by c-myc translocation and is CD10+, bcl-6+, bcl-2– with a very high Ki-67 proliferation index. Occasion­al diffuse large B-cell lymphomas may exhibit a very high proliferation index with or without a starry-sky pattern (DLBCL-HPSS). The authors compared 28 consecutive cases of Burkitt lymphoma and 16 cases of DLBCL-HPSS in immuno—competent Taiwanese. The subjects were diagnosed by histopathologic examination and immunophenotyping and the results compared with results for Epstein-Barr virus-encoded messenger RNA (EBER) and fluorescence in situ hybridization (FISH). The authors found statistically significant differences in the expression of CD10 (28/28 versus 1/16), bcl-2 (3/28 versus 11/16), and MUM1 (5/28 versus 15/16), a proliferation index of 95 percent or more (27/28 versus 2/16), and combined CD10+/ bcl-2–/bcl-6+ (24/28 versus 1/16) between cases of Burkitt lymphoma and DLBCL-HPSS. Of the Burkitt lymphomas, seven (25%) of 28 and 26 (96%) of 27 were positive for EBER and c-myc rearrangement as compared with zero of 16 and one (7%) of 15 DLBCL-HPSSs, respectively. The authors concluded that Burkitt lymphoma can be distinguished from DLBCL-HPSS using histopathologic and immunohistochemical (CD10, bcl-2, bcl-6, Ki-67) methods, without the aid of EBER and FISH in the majority of cases.

Chuang SS, Ye H, Du M, et al. Histopathology and immunohistochemistry in distinguishing Burkitt lymphoma from diffuse large B-cell lymphoma with very high proliferation index and with or without a starry-sky pattern: a comparative study with EBER and FISH. Am J Clin Pathol. 2007; 128: 558– 564.

Reprints: Dr. S. S. Chuang, Dept. of Pathology, Chi-Mei Medical Center, 901 Chung-Hwa Rd., Yung-Kang City, Tainan County 710, Taiwan
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Immunostaining in atypical immature squamous metaplasia of uterine cervix Immunostaining in atypical immature squamous metaplasia of uterine cervix

Atypical immature squamous metaplasia of the cervix is a loosely defined entity characterized by immature metaplastic cells with mild cytologic atypia. The authors conducted a study to examine whether a combination of immuno­staining for p16 and Ki-67 could be used to stratify atypical immature squamous metaplasia (AIM) cases into the categories of benign, nondiagnostic atypia, and high-grade squamous intraepithelial lesion (HSIL). The study consisted of 37 cases of AIM, 23 of benign cervical mucosa (NEG), and 36 of HSIL. All cases were tested for high-risk human papillomaviruses using SPF 10 polymerase chain reaction and immunostained for p16 and Ki-67. All cases of HSIL were positive for p16 and Ki-67. All but two benign control cases were negative for p16 and Ki-67. Seven cases of AIM (19%) displayed a pattern of immuno­staining identical to HSIL, and these most likely represent a spectrum of HSIL. A total of 54 percent of cases of AIM were negative for p16 and Ki-67, consistent with benign reactive atypia. Two AIM cases (5%) were negative for p16 and positive for Ki-67 in the area adjacent to an ulcer, representing regeneration. Finally, 22 percent of AIM cases were positive for p16 and negative for Ki-67. These cases may represent a precursor of HSIL or, alternatively, a regressing HSIL. The authors concluded that the combination of immunostaining for p16 and Ki-67 is helpful in limiting the number of cases with nondiagnostic atypia of the cervix.

Iaconis L, Hyjek E, Ellenson LH, et al. P16 and Ki-67 immunostaining in atypical immature squamous metaplasia of the uterine cervix: correlation with human papillomavirus detection. Arch Pathol Lab Med. 2007; 131: 1343– 1349.

Reprints: Dr. Edyta C. Pirog, Dept. of Pathology, Weill Medical College of Cornell University, 525 E. 68th St., F-766, New York, NY 10021; ecpirog@mail.med.cornell.edu
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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.