CAP TODAY Pathology/Laboratory Medicine/Laboratory Management
Oncotype DX recurrence score: use of pathology-generated equations from linear regression analysis
Oncotype DX is a commercial assay frequently used to make decisions about chemotherapy in estrogen receptor-positive breast cancers. The result is reported as a recurrence score ranging from zero to 100 and divided into low-risk (<18), intermediate-risk (18–30), and high-risk (≥31) categories. The authors conducted a pilot study that showed that recurrence score can be predicted by an equation that incorporates standard morphoimmunohistologic variables (referred to as the original Magee equation). Using a data set of 817 cases, the authors formulated three additional equations (referred to as new Magee equations one, two, and three) to predict the recurrence score category for an independent set of 255 cases. The concordance between the risk category of Oncotype DX and the authors’ equations was 54.3 percent, 55.8 percent, 59.4 percent, and 54.4 percent for the original Magee equation and new Magee equations one, two, and three, respectively. When the intermediate category was eliminated, the concordance increased to 96.9 percent, 100 percent, 98.6 percent, and 98.7 percent for the original Magee equation and new Magee equations one, two, and three, respectively. Even when the estimated recurrence score fell in the intermediate category with any of the equations, the actual recurrence score was intermediate or low in more than 80 percent of the cases. The authors concluded that any of the four equations can be used to estimate the recurrence score, depending on available data. If the estimated recurrence score is clearly high or low, oncologists should not expect a dramatically different result from the Oncotype DX test, and the test may not be needed. Conversely, an Oncotype DX result that is dramatically different from what is expected based on standard morphoimmunohistologic variables should be thoroughly investigated.
Klein ME, Dabbs DJ, Shuai Y, et al. Prediction of the Oncotype DX recurrence score: use of pathology-generated equations derived by linear regression analysis. Mod Pathol. 2013;26:658–664.
Correspondence: Dr. R. Bhargava at rbhargava@mail.magee.edu
Neuroendocrine carcinoma of the stomach: characteristics and prognosis
Neuroendocrine carcinoma of the stomach has been recognized as a highly malignant tumor. However, because it is rare, limited information is available regarding its clinicopathologic characteristics. The authors investigated the morphologic and immunohistochemical features and prognoses of 51 cases of gastric neuroendocrine carcinoma. Histologically, 40 lesions were large cell type and 11 were small cell type. The vast majority of the tumors exhibited a solid growth pattern (94 percent), with subsets of tumors showing trabecular (18 percent), scirrhous (10 percent), or tubular (six percent) growth patterns. Thirty-six cases (71 percent) had adenocarcinoma components or dysplasia, or both. Of those, 26 cases (51 percent) were associated with intramucosal adenocarcinoma or dysplasia. Immunohistochemically, synaptophysin, chromogranin A, and CD56 were diffusely expressed in 48 (94 percent), 44 (86 percent), and 24 (47 percent) cases, respectively. Two recently reported neuroendocrine markers, ASH1 and NKX2.2, were diffusely positive in 12 (24 percent) and 17 (33 percent) cases, respectively. The diffuse or focal expression of TTF-1 was observed in 19 cases (37 percent). Among the 41 patients who underwent curative resection, 16 patients (39 percent) developed radiologic recurrences, and the liver was the most frequent site of recurrence (11 patients; 27 percent). The three- and five-year overall survival rates were 57.8 percent and 44.7 percent, respectively. None of the histologic subclassifications, including small cell versus large cell types and the presence versus absence of adenocarcinoma components and/or dysplasia, were significant with regard to patient outcome. Curative surgery was identified as the sole independent prognostic factor in a multivariate analysis (P=0.03). The authors concluded that although gastric neuroendocrine carcinomas exhibit significant morphologic diversity, their histologic subclassification is unlikely to be of immediate clinical relevance.
Ishida M, Sekine S, Fukagawa T, et al. Neuroendocrine carcinoma of the stomach: morphologic and immunohistochemical characteristics and prognosis. Am J Surg Pathol. 2013;37(7):949–959.
Correspondence: Dr. Shigeki Sekine at sse kine@ncc.go.jp
Interobserver reproducibility in diagnosis of high-grade endometrial carcinoma
Patients with high-grade subtypes of endometrial carcinoma—grade 3 endometrioid, serous, clear cell, or carcinosarcoma—have a relatively poor prognosis. The specific subtype may be used to guide patient management, but little information exists regarding the reproducibility of subtype diagnoses in cases of high-grade endometrial carcinoma. Consequently, the authors undertook a study in which 56 cases diagnosed as a high-grade subtype of endometrial carcinoma were identified from the pathology archives of Vancouver (Canada) General Hospital. All slides for each case were reviewed independently by three pathologists, who diagnosed the specific tumor subtypes and assigned the percentage of each subtype for mixed tumors. Agreement between observers was categorized as major or minor. Major disagreement was no consensus for low-grade endometrioid versus high-grade carcinoma (any subtype) or no consensus with respect to the predominant high-grade subtype present. Minor disagreement was when a consensus was reached about the cell type of the predominant component of a mixed tumor but there was disagreement about the subtype of the minor component. A tissue microarray was constructed from these cases and immunostained for p16, estrogen receptor, progesterone receptor, PTEN, and p53. In 35 of 56 cases (62.5 percent), there was agreement between all three reviewers regarding the subtype diagnosis of the exclusive (in pure tumors) or predominant (in mixed tumors) high-grade component. Minor disagreement occurred in four of the cases (7.1 percent). In 20 of 56 cases (35.8 percent), there was major disagreement. In 17 (30.4 percent) of the latter, there was no consensus about the major subtype diagnosis, and in three cases (5.4 percent), there was disagreement about whether a component of high-grade endometrial carcinoma was present. All three reviewers diagnosed the final case as low-grade endometrioid carcinoma, disagreeing with the original diagnosis of high-grade carcinoma. The most frequent areas of disagreement were serous versus clear cell (seven cases) and serous versus grade 3 endometrioid (six cases). Immunostaining results using the five-marker immunopanel were then used to adjudicate in the six cases in which there was disagreement between reviewers with respect to serous versus endometrioid carcinoma. These supported a diagnosis of serous carcinoma in four of six cases and endometrioid carcinoma in two of six cases. With regard to pairwise comparisons between the reviewers for the 20 cases classified as showing major disagreement, reviewers one and two agreed in five of 20 cases, reviewers one and three agreed in seven of 20 cases, and reviewers two and three agreed in eight of 20 cases, indicating that disagreements were not because of a single reviewer with outlier opinions. Diagnostic consensus among the three reviewers about the exclusive or major subtype of high-grade endometrial carcinoma was reached in only 35 of 56 cases (62.5 percent), and in four of the cases there was disagreement about the minor component present. This poor reproducibility did not reflect systematic bias on the part of any one reviewer. The authors concluded that molecular tools are needed to aid in the accurate and reproducible diagnosis of high-grade endometrial carcinoma subtype.
Gilks CB, Oliva E, Soslow RA. Poor interobserver reproducibility in the diagnosis of high-grade endometrial carcinoma. Am J Surg Pathol. 2013;37(6):874–881.
Correspondence: Dr. C. Blake Gilks at blake.gilks@vch.ca
Features associated with metastatic potential in invasive adenocarcinomas of the lung
The International Association for the Study of Lung Cancer (IASLC) recently reclassified adenocarcinomas of the lung on the basis of histologic patterns. However, consensus about a grading system for these tumors is lacking. The authors studied a series of invasive lung adenocarcinomas and correlated histologic features with lymph node and distant metastases. A series of invasive lung carcinomas resected over a five-year period were retrospectively reviewed and classified by the IASLC system. The proportion of each histologic subtype was estimated at five percent increments, and cytologic features were blindly recorded and subsequently correlated with lymph node and distant metastases. The 125 tumors were classified on the basis of the predominant pattern as lepidic predominant (n=9), acinar (n=71), solid (n=23), papillary (n=11), and mucinous (n=11). The acinar pattern was heterogeneous in that a cribriform subgroup (n=34) was significantly more likely to demonstrate lymph node metastases compared with a tubular subgroup (n=37) and had a higher mitotic rate and rate of necrosis, as well as vascular invasion and prominent nucleoli. Mucinous tumors were lepidic predominant (n=3), tubular (n=4), and cribriform predominant (n=4). The rate of lymph node metastasis was greatest in the solid type (P=0.02), and the rate of distant metastasis was greatest in the mucinous and solid groups (P<0.02). Mitotic activity (one high-power field or greater), desmoplasia greater than 20 percent of the tumor, prominent nucleoli, and vascular invasion, along with a solid growth pattern of 20 percent or more, were independently associated with metastatic potential and considered poor prognostic histologic features. A three-tiered grading system separated tumors into well differentiated (predominantly lepidic predominant, papillary, and tubular patterns), moderately differentiated (predominantly cribriform tumors), and poorly differentiated (20 percent or greater solid growth pattern). Tumors in the well-differentiated group were elevated to moderately differentiated if they had poor prognostic histologic features. Using this system, there was a stepwise increase in the rate of lymph node metastasis (P<0.0001) and distant metastasis (P=0.0004) from well-differentiated, moderately differentiated, to poorly differentiated tumors, the rate being 40, 46, and 39, respectively. Application of the IASLC classification in this series resulted in a predominance of acinar adenocarcinomas. The authors concluded that to stratify tumors into clinically relevant grades, it is useful to grade by pattern (tubular, cribriform, solid), mitotic activity, and nuclear features.
Xu L, Tavora F, Burke A. Histologic features associated with metastatic potential in invasive adenocarcinomas of the lung. Am J Surg Pathol. 2013;37(7):1100–1108.
Correspondence: Dr. Allen Burke at allen.burke@gmail.com