Accurate diagnosis of metastatic germ-cell tumors is critical because these tumors can be treated, and even cured, with modern therapy. Histopathologic diagnosis of such tumors can be challenging without immunohistochemical markers, and these markers have limitations. SALL4 is a novel stem-cell marker essential to maintaining pluripotency and self-renewal of embryonic stem cells. The authors conducted a study in which they investigated the utility of SALL4 as a potential diagnostic marker for metastatic germ-cell tumors. For the study, 90 metastatic germ-cell tumors from testis, ovary, and extragonadal sites were stained with a monoclonal SALL4 antibody. In addition, 170 metastatic nongerm-cell malignancies, including 158 carcinomas (6 head and neck, 8 thyroid, 12 lung, 8 breast, 7 hepatocellular, 3 cholangiocarcinomas, 2 ampullary, 10 pancreatic, 18 gastric, 15 esophageal, 10 renal cell, 10 urothelial, 12 prostatic, 18 ovarian, 6 uterine, and 13 colonic) and 12 mela-nomas were also stained to test the specificity of SALL4. The authors found that all 22 seminomas, seven dysgerminomas, 22 embryonal carci-nomas, and 14 of 15 yolk sac tumors displayed strong and diffuse SALL positivity in more than 90 percent of tumor cells. (Eighty percent of tumor cells were strongly positive in the remaining yolk sac tumor.) Five of seven choriocarcinomas and nine of 18 teratomas were also variably positive for SALL4. In contrast, only 10 of 170 metastatic somatic tumors (esophageal, gastric, and colonic adenocarcinomas) demonstrated focally weak SALL4 reactivity (less than 25 percent of tumor cells). The authors concluded that SALL4 is a novel, sensitive, and highly specific marker for metastatic germ-cell tumors and is particularly useful for detecting metastatic yolk sac tumors.
Cao D, Humphrey PA, Allan RW. SALL4 is a novel sensitive and specific marker for metastatic germ cell tumors, with particular utility in detection of metastatic yolk sac tumors. Cancer. 2009;115(12):2640–2651.
Correspondence: Dr. Dengfeng Cao at firstname.lastname@example.org
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Malignancies found in unexpected locations or with poorly differentiated morphologies can pose a significant challenge for tissue-of-origin determination. Histologic and imaging techniques do not definitively identify the tissue of origin in a significant number of cases. The authors conducted a study to validate a predefined 1,550-gene-expression profile for this purpose. For the study, four institutions processed 547 frozen specimens, representing 15 tissues of origin, using oligonucleotide microarrays. Half of the specimens were metastatic tumors, and the remainder were poorly differentiated and undifferentiated primary cancers chosen to resemble those that present as a clinical challenge. The authors found that in this blinded multicenter validation study, the 1,550-gene-expression profile was highly informative in tissue determination. Over-all sensitivity (positive percent agreement with reference diagnosis) was 87.8 percent (95 percent confidence interval [CI], 84.7 percent to 90.4 percent), and overall specificity (negative percent agreement with reference diagnosis) was 99.4 percent (95 percent CI, 98.3 percent to 99.9 percent). Performance within the subgroup of metastatic tumors (n=258) was found to be slightly lower than in the poorly differentiated and undif-ferentiated primary tumor subgroup—84.5 percent and 90.7 percent, respectively (P=.04). Differences between individual laboratories were not statistically significant. The authors concluded that this study represents the first adequately sized, multicenter validation of a gene-expression profile for tissue-of-origin determination restricted to poorly differentiated and undifferentiated primary cancers and metastatic tumors. This profile should be a valuable addition or alternative to other diagnostic methods for evaluating uncertain primary cancers.
Monzon FA, Lyons-Weiler M, Buturovic LJ, et al. Multicenter validation of a 1,550-gene expression profile for identification of tumor tissue of origin. J Clin Oncol. 2009;276:2503–2508.
Correspondence: Dr. Federico A. Monzon at email@example.com
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Tumor stage and grade for gastrointestinal stromal tumors are poorly defined. To develop a better evaluation system, the authors assessed 12 clinical and pathological parameters for 613 patients with followup information. The parameters were classified into two gross spread parameters, including liver metastasis and peritoneal dissemination; five microscopic spread parameters, including lymph node metastasis, vascular, fat, nerve, and mucosal infiltration; and five histological parameters, including mitotic count of 10 per 50 high-power fields or greater, muscularis propria infiltration, coagulative necrosis, perivascular pattern, and severe nuclear atypia. The five-year disease-free survival and overall survival rates for 293 patients without any of these predictive parameters of malignancy were 99 percent and 100 percent, respectively. The tumors were regarded as nonmalignant, and no further evaluations of the stage and grade of the tumors were performed. At least one, and at most seven, predictive parameters of malignancy were identified in 320 patients. For those patients, the five-year disease-free survival and overall survival rates were 44 percent (mean, 6.7 years) and 60 percent (mean, 9.3 years), respectively. The disease-free survival rates showed significant differences between patients with and without gross spread (P<.0001), with and without microscopic spread (P=.0009). Disease-free survival and overall survival were associated with the number of predictive parameters of malignancy in patients without gross spread (P<.0001 for disease-free and overall survival), but not in patients with gross spread (P=.882 and P=.441, respectively). Malignant gastrointestinal stromal tumors could be divided into clinical stages I and II based on the absence and presence of gross spread, respectively. The degree of malignancy of patients in clinical stage I could be graded according to the number of predictive parameters of malignancy. Patients in clinical stage II were of the highest degree of malignancy, regardless of the number of parameters. The authors determined that clinical stage and grade were strongly associated with prognosis.
Hou YY, Lu SH, Zhou Y, et al. Stage and histological grade of gastrointestinal stromal tumors based on a new approach are strongly associated with clinical behaviors. Mod Pathol. 2009;22(4):556–569.
Correspondence: Dr. Y. Y. Hou at firstname.lastname@example.org
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Matrix-producing carcinoma of the breast is a subtype of metaplastic carcinoma defined as an invasive breast carcinoma with a direct transi-tion of carcinoma to cartilaginous or osseous matrix without an intervening spindle cell component. The authors conducted a study to evaluate specific histologic characteristics of matrix-producing carcinoma (MPC) and correlate these with disease recurrence and to determine whether rates of locoregional and distant recurrence for MPC are significantly different from those for invasive ductal carcinoma. They identified 32 cases of MPC. Fourteen patients (44 percent) were 50 years old or younger; 10 (31 percent) had tumors of 2 cm or less; and six (19 percent) had tumors of 5 cm or more. All tumors contained chondromyxoid or chondroid matrix, and one (3.1 percent) also contained focal (less than five percent) osseous matrix. High-grade matrix was present in nine cases (28 percent), and low-grade matrix was present in 23 (72 percent). Matrix constituted 10 percent or less of the tumor in 14 cases (44 percent), between 10 percent and 40 percent in nine (28 percent), and 40 percent or more in nine (28 percent). The carcinomatous component was high grade in 30 cases (94 percent), and 19 tumors (59 percent) had central necro-sis. Seven patients (22 percent) had positive axillary lymph nodes, and eight (25 percent) had lymphovascular space invasion. LVSI was the only factor independently associated with locoregional recurrence-free survival in multivariate analysis (P=.043). Although 40 percent or greater matrix was associated with improved distant recurrence-free survival in univariate analysis (P=.044), only LVSI and tumor stage were independ-ently associated with distant recurrence-free survival in multivariate analysis (P=.027 and P=.001, respectively). Compared with matched con-trols with invasive ductal carcinoma, patients with MPC had decreased locoregional recurrence-free survival (P=.001) and decreased distant recurrence-free survival (P=.001). The authors concluded that MPC is an aggressive subtype of metaplastic carcinoma with a worse clinical out-come than invasive ductal carcinoma.
Downs-Kelly E, Nayeemuddin KM, Albarracin C, et al. Matrix-producing carcinoma of the breast: an aggressive subtype of metaplastic carcinoma. Am J Surg Pathol. 2009;33(4):534–541.
Correspondence: Dr. Michael Z. Gilcrease at email@example.com
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Anatomic pathology abstracts editors: Michael Cibull, MD, professor and vice chair, Department of Pathology and Laboratory Medicine, University of Kentucky College of Medicine, Lexington; Melissa Kesler, MD, and Rouzan Karabakhtsian, MD, assistant professors of pathology and laboratory medicine, University of Kentucky College of Medicine; and Megan Zhang, MD, visiting fellow, Division of Dermatopathology, University of California, San Francisco.