CAP TODAY Pathology/Laboratory Medicine/Laboratory Management
Anatomic pathology abstracts editors: Michael Cibull, MD, professor and vice chair, Department of Pathology and Laboratory Medicine, University of Kentucky College of Medicine, Lexington; Rouzan Karabakhtsian, MD, attending pathologist, Department of Pathology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY; and Thomas Cibull, MD, dermatopathologist, Evanston Hospital, NorthShore University HealthSystem, Evanston, Ill.
Prolonged cold ischemia time and ER immunohistochemistry in breast cancer
To aid detection of estrogen receptor expression in breast tumors, the American Society of Clinical Oncology and College of American Pathologists recommend that cold ischemia time be kept under one hour. However, data to address the upper threshold of cold ischemia time are limited. Although it is routine practice at the authors’ institution to keep cold ischemia time under one hour for breast core biopsy specimens, this is difficult for surgical specimens because of the comprehensive intraoperative assessment performed at the authors’ institution. The authors conducted a retrospective study in which they compared estrogen receptor (ER) immunohistochemical staining results in paired breast tumor core biopsy specimens and resection specimens with cold ischemia times ranging from 64 to 357 minutes in 97 patients. The staining category (10 percent or more, positive; one percent to nine percent, low positive; less than one percent, negative) between the core biopsy and resection specimens changed for five patients (five percent). The weighted kappa statistic for ER staining category between the two specimen types was 0.86 (95 percent confidence interval, 0.74–0.99), indicating good concordance. The difference in the percentage of ER staining between core biopsy and resection was not significantly associated with cold ischemia time (P=.81, Spearman correlation). Although the authors did not observe significant associations between the difference in ER staining in the two specimen types and cold ischemia time after placing the patients in the three groups of “increase,” “decrease,” and “no change” using a difference of 25 percent in ER staining percentage as the cutoff, a trend of decreased ER staining with cold ischemia time of more than two hours was detected. No statistically significant association was found between change of ER staining and history of neoadjuvant chemotherapy. These findings indicate that a prolonged cold ischemia time of up to four hours (97 percent of this cohort) in the practice setting of the authors’ institution has minimal clinical impact on ER immunohistochemical expression in breast tumors.
Li X, Deavers MT, Guo M, et al. The effect of prolonged cold ischemia time on estrogen receptor immunohistochemistry in breast cancer. Mod Pathol. 2013;26:71–78.
Correspondence: Dr. L. Huo at leihuo@mdanderson.org
Interobserver reliability in diagnosis of cartilaginous tumors in patients with multiple osteochondromas
Distinguishing between benign and malignant cartilaginous tumors located peripherally in the bone may be a challenging task in surgical pathology. The authors conducted a study to investigate interobserver reliability in the histological diagnosis of cartilaginous tumors in the setting of multiple osteochondromas and to evaluate possible histological parameters that could differentiate among osteochondroma and low- and high-grade secondary peripheral chondrosarcoma. For the study, 12 specialized bone-tumor pathologists assessed interobserver reliability in a set of 38 cases. Substantial agreement on diagnosis among all the reviewers was observed (intraclass correlation coefficient, 0.78). This study confirmed that mitotic figures and nuclear pleomorphism are hallmarks of high-grade secondary peripheral chondrosarcoma. However, despite substantial agreement, the authors demonstrated that histology alone cannot distinguish osteochondroma from low-grade secondary peripheral chondrosarcoma in the setting of multiple osteochondromas, as nodularity, presence of binucleated cells, irregular calcification, cystic/mucoid changes, and necrosis were not helpful in indicating malignant transformation of an osteochondroma. On the other hand, among the concordant cases, the cartilage cap in osteochondroma was significantly less thick than in low- and high-grade secondary peripheral chondrosarcoma. Therefore, the authors concluded that their study shows that a multidisciplinary approach that integrates clinical and radiographical features and the size of the cartilaginous cap, in combination with a histological assessment, are crucial to the diagnosis of cartilaginous tumors.
De Andrea CE, Kroon HM, Wolterbeek R, et al. Interobserver reliability in the histopathological diagnosis of cartilaginous tumors in patients with multiple osteochondromas. Mod Pathol. 2012;25:1275–1283.
Correspondence: Dr. J. V. Bovée at j.v.m.g.bovee@lumc.nl
High proliferation associated with inferior outcome in male breast cancer patients
Assessment of proliferation is important in female breast cancer, and treatment decisions are based on its results, especially in the luminal subgroups. Gene-expression analyses fail to group male breast cancer into the intrinsic subgroups established for female breast cancer. Even though proliferation has been shown to divide male breast cancer into molecular subgroups with different prognoses, the clinical importance of proliferation markers has not been elucidated. Previous studies of male breast cancer have demonstrated contradictory results regarding the prognostic impact of histological grade and Ki-67, parameters strongly associated with proliferation. The authors studied proliferation in male breast cancer by assessing other proliferation-related markers, namely cyclins A, B, and D1, and mitotic count. They investigated 197 male breast cancer cases with accessible paraffin-embedded material and outcome data and performed immunohistochemical stainings on tissue microarrays. Kaplan-Meier estimates and Cox proportional regression models were used for survival analyses, with breast cancer death as the event. The subset of patients with high expression of cyclin A (hazard ratio [HR], 3.7; P=.001) and B (HR, 2.7; P=.02) demonstrated a poorer survival. Furthermore, high mitotic count was associated with an increased risk of breast cancer death (HR, 2.5; P=.01). In contrast, cyclin D1 overexpression was predictive of better breast cancer survival (HR, 0.3; P=.001). The authors concluded that high levels of cyclin A and B expression and an elevated mitotic count result in a two- to threefold higher risk for breast cancer death, whereas cyclin D1 overexpression halves the risk. The clinical utility of these proliferation markers needs to be clarified further.
Nilsson C, Koliadi A, Johansson I, et al. High proliferation is associated with inferior outcome in male breast cancer patients. Mod Pathol. 2013;26:87–94.
Correspondence: Dr. C. Nilsson at cecilia.nilsson@ltv.se or cessan.nilsson@telia.com
Relevance of number of examined lymph nodes in gastric cancer
The seventh edition of the tumor, lymph node, metastasis staging system increased the required number of examined lymph nodes in gastric cancer from 15 to 16. However, the same staging system defines lymph node-negative gastric cancer regardless of the number of examined nodes. The authors conducted a study in which they evaluated whether gastric cancer can be staged properly with fewer than 15 examined lymph nodes. They analyzed the survival rates of 10,010 patients who underwent curative gastrectomy from 1987 to 2007. The patients were divided into two groups according to the number of examined lymph nodes: an “insufficient” group (15 or fewer examined nodes) and a “sufficient” group (16 or more examined nodes). The survival curves of patients from both groups were compared according to the seventh edition of the tumor-node-metastasis (TNM) classification. Three hundred sixteen patients (3.2 percent) had 15 or fewer examined lymph nodes for staging after they underwent standard, curative lymphadenectomy. The authors found that patients who had T1 tumor classification, N0 lymph node status, and stage I disease with an insufficient number of examined lymph nodes after curative gastrectomy had a significantly worse prognosis than patients who had 16 or more examined nodes. Moreover, having an insufficient number of examined lymph nodes was an independent prognostic factor for patients who had T1, N0, and stage I disease. The authors concluded that lymph node-negative cancers in which 15 or fewer lymph nodes were examined, classified as N0 in the new TNM staging system, could not adequately predict patient survival after curative gastrectomy, especially in patients with early stage gastric cancer.
Son T, Hyung WJ, Lee JH, et al. Clinical implication of an insufficient number of examined lymph nodes after curative resection for gastric cancer. Cancer. 2012;118:4687–4693.
Correspondence: Dr. Sung Hoon Noh at sunghoonn@yuhs.ac