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.
Diagnostic and prognostic morphometric features in WHO 2003 invasive endometrial stromal tumors
The authors conducted a study to determine the value of morphometric features in distinguishing between mild and moderate atypia and predicting the recurrence of World Health Organization 2003-defined endometrial stromal sarcoma and highly malignant undifferentiated endometrial sarcoma. For the study, nuclear and cytological size, shape, and arrangement were morphometrically evaluated in 41 cases with a consensus of no/mild atypia (n=38) or moderate atypia (n=3). None of the cases showed necrosis. The authors also assessed the prognostic value of these features in predicting recurrence. Seven features differed. The mean and standard deviation of the nuclear volume and distance between nuclei were the best discriminators between no/mild atypia and moderate atypia, with the maximum of the nuclear volume being a practical and rapidly evaluable alternative. With the use of these features, all mild and moderate atypias were classified correctly. Seven cases recurred. The distance between the nuclei and the percentage of nuclei with one neighbor (assessed with morphometric minimum spanning tree analysis) predicted recurrence. The authors concluded that in invasive endometrial stromal tumors, morphometric features are useful diagnostic support tools for distinguishing mild from moderate atypia and predicting recurrence.
Feng W, Malpica A, Yinhua Y, et al. Diagnostic and prognostic morphometric features in WHO2003 invasive endometrial stromal tumours. Histopathology. 2013;62:688–694.
Correspondence: jingsakura@gmail.com
Association of tumor staging with adverse clinical outcome in neuroendocrine tumors of appendix
Appendiceal neuroendocrine neoplasms are rare and are usually discovered incidentally. While most cases are clinically indolent, the rare aggressive ones are difficult to predict. The authors conducted a study to test the applicability and prognostic significance of the new World Health Organization classification and the several pathologic features and tumor-node-metastasis staging systems (American Joint Committee on Cancer and European Neuroendocrine Tumor Society) in these tumors. A multi-institutional retrospective series of 138 appendiceal neuroendocrine neoplasms (NENs) was selected on the basis of the availability of pathologic material and clinical information, including followup data. All cases were reviewed to record pathologic features and to apply year 2000 and 2010 WHO classifications, as well as European Neuroendocrine Tumor Society and American Joint Committee on Cancer TNM stages. Clinical and pathologic characteristics were compared with disease outcome by contingency, univariate, and multivariate survival analyses. Although up to one-third of cases presented several malignancy-associated pathologic features, only four patients died of the disease. Adverse outcome was significantly associated with extramural extension, including mesoappendix, well-differentiated carcinoma diagnosis (2000 WHO classification), pT3-4 stage, older age, and presence of positive resection margins, but not with tumor size, mitotic or proliferative indices, and, consequently, 2010 WHO grading. The authors concluded that in the appendix, at variance with midgut/hindgut NENs, the 2000 WHO classification performs better than the grading-based 2010 WHO scheme and, with tumor stage, is the most relevant parameter associated with clinical aggressiveness.
Volante M, Daniele L, Asioli S, et al. Tumor staging but not grading is associated with adverse clinical outcome in neuroendocrine tumors of the appendix: a retrospective clinical pathologic analysis of 138 cases. Am J Surg Pathol. 2013;37(4): 606–612.
Correspondence: Dr. Marco Volante at marco.volante@unito.it
Detection of HPV capsid proteins L1 and L2 in squamous intraepithelial lesions
hile cervical cancer screening relies on cervical cytology and high-risk human papillomavirus detection, histologic diagnosis, and specifically lesion grade, is the main parameter that drives clinical management of screen-positive women. Morphologically diagnosed squamous intraepithelial lesions (SIL/CIN) regress spontaneously in more than half of cases, but identifying those likely to persist and progress is not possible based on morphology. Lack of major capsid protein L1 expression has been suggested as a feature in progressive lesions, whereas expression of the minor capsid protein L2 has not been evaluated extensively. The authors conducted a study to evaluate the immunohistochemical expression of L1 and L2 in correlation with lesion grade in SILs. A total of 150 cervical specimens with SILs were selected based on HPV 16 or HPV 18 detection by quantitative polymerase chain reaction. These included 89 low-grade SILs (LSIL/CIN 1) and 123 high-grade SILs (75 HSIL/CIN 2 and 48 HSIL/CIN 3). More than one lesion/grade was identified in 53 specimens. The presence and grade of SIL were determined by a panel of pathologists. Capsid protein expression was assessed by immunohistochemistry using MAB 837 for L1 and RG-1 for L2. Lesions of different grades in the same specimen were scored separately. Expression of capsid proteins was detected in 34 of 89 (40 percent) LSIL/CIN 1, five of 75 (six percent) HSIL/CIN 2, and none of 48 HSIL/CIN 3. L1 and L2 were co-expressed in the same area of the lesion in 22 cases. In addition, L1 alone was expressed in six lesions and L2 alone in 11 lesions. Among the cases with multiple lesion grades in the same specimen, none with HSIL/CIN 3 expressed capsid proteins in any portion/grade of the lesion. The authors concluded that HPV capsid proteins are expressed almost exclusively in LSIL/CIN 1 and rarely in HSIL/CIN 2. Additional studies are warranted to examine lack of L1 and L2 expression in LSIL/CIN 1 as a predictor of persistence or progression to HSIL/CIN 3, the precursor of cervical cancer.
Yemelyanova A, Gravitt PE, Ronnett BM, et al. Immunohistochemical detection of human papillomavirus capsid proteins L1 and L2 in squamous intraepithelial lesions: potential utility in diagnosis and management. Mod Pathol. 2013;26:268–274.
Correspondence: Dr. A. Yemelyanova at ayemely1@jhmi.edu
Feasibility and safety of sequential research-related tumor core
biopsies in clinical trials
Interest in serial research biopsies in studies of targeted therapies is increasing. A definition of patient characteristics and optimal target tissue for safe research tumor biopsy in the era of antiangiogenic and targeted agents is needed. The authors conducted an institutional review board-approved, retrospective study that included chart and interventional radiology case review from six phase I/II studies at the National Cancer Institute. One hundred forty-two of 150 protocol patients who were approached for the study gave consent for research biopsies. Patients were a median age of 56 years (range, 27–78 years) and had a median body mass index of 25.8 kg/m2 (range, 14.4–46.2 kg/m2). They also had an Eastern Cooperative Oncology Group performance status of zero or one and normal end-organ function. Baseline biopsies were collected from 138 of 142 patients (97 percent), and paired specimens were collected from 96 (70 percent). Most patients had metastatic gynecologic cancers (85 percent), and 78 percent had target disease below the diaphragm with a median size of 2.7 cm (range, 1–14.5 cm). Protocol therapies included kinase inhibitors (35 percent), angiogenesis inhibitors (54 percent), and olaparib/carboplatin (11 percent). Therapy was not interrupted for biopsies. All adverse events were uncomplicated and observed in four patients (liver subcapsular hematoma in one patient, vasovagal syncope in two patients, and pneumothorax in one patient). The complication rate in obese patients was similar to that in nonobese patients (three of 108 patients versus one of 34 patients, respectively). Sixty-seven patients (48 percent) were receiving bevacizumab at the time of subsequent biopsies. The complication rate was not different between patients who were and were not receiving bevacizumab (three of 67 patients versus one of 71 patients, respectively). Ninety-five percent of biopsies yielded useable material. The authors concluded that serial percutaneous core-needle biopsies can be obtained safely and yield material applicable for multiple translational applications. Obesity or concomitant antiangiogenic therapy, or both, and depth of disease did not increase the risk of complications or preclude the acquisition of useful tissue.
Lee JM, Hays JL, Noonan AM, et al. Feasibility and safety of sequential research-related tumor core biopsies in clinical trials. Cancer. 2013;119:1357–1364.
Correspondence: Dr. J. M. Lee at leej6@mail.nih.gov