Anatomic Abstracts
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October 2012 Editors:
Atypical apocrine adenosis is a rare breast lesion in which the cellular population demonstrates cytologic alterations that may be confused with malignancy. The clinical significance and management of atypical apocrine adenosis are unclear because of the lack of long-term followup studies. The authors attempted to determine the breast cancer risk in a retrospective series of patients with atypical apocrine adenosis diagnosed in otherwise benign breast excisional biopsies. They identified 37 atypical apocrine adenosis cases in the Mayo Benign Breast Disease Cohort (9,340 women) between 1967 and 1991 with a blinded pathology re-review. Breast cancer diagnoses subsequent to initial atypical apocrine adenosis biopsy were identified (average followup, 14 years). The mean age at diagnosis of atypical apocrine adenosis in the group was 59 years. Breast carcinoma subsequently developed in three women (eight percent) with atypical apocrine adenosis and was diagnosed after followup intervals of four, 12, and 18 years. The tumor from one of the three cases (33 percent) was ductal carcinoma in situ, contralateral to the original biopsy, and the other two cases (66 percent) were invasive carcinoma. Ages at the time of diagnosis of atypical apocrine adenosis were 55, 47, and 63 years for those that developed in situ or invasive carcinoma. The authors concluded that this study supports the contention that atypical apocrine adenosis was a rare lesion during the accrual era of their cohort (fewer than one percent of cases); women found to have atypical apocrine adenosis were, on average, older than were other women with benign breast disease—yet there does not seem to be an association with age and risk of developing carcinoma in patients diagnosed with atypical apocrine adenosis, as previously suggested; and atypical apocrine adenosis does not appear to be an aggressive lesion and should not be regarded as a direct histologic precursor to breast carcinoma. Fuehrer N, Hartmann L, Degnim A, et al. Atypical apocrine adenosis of the breast: long-term follow-up in 37 patients. Arch Pathol Lab Med. 2012;136(2):179–182. Correspondence: Dr. Daniel Visscher at visscher.daniel@mayo.edu
Epithelioid mesothelioma is the most prevalent subtype of diffuse malignant pleural mesothelioma in which only staging is prognostic for survival. The authors conducted a study of epithelioid diffuse malignant pleural mesothelioma in which they investigated the prognostic utility of nuclear features. They reviewed the slides of 232 epithelioid diffuse malignant pleural mesothelioma patients (14 stage I, 54 stage II, 130 stage III, and 34 stage IV) from a single institution to assess the following seven nuclear features: nuclear atypia, nuclear/cytoplasmic ratio, chromatin pattern, intranuclear inclusions, prominence of nucleoli, mitotic count, and atypical mitoses. They performed MIB-1 immunohistochemistry using tissue microarray and recorded MIB-1 labeling index as the percentage of positive tumor cells. Median overall survival for all patients was 16 months and correlated with nuclear atypia (P<.001), chromatin pattern (P=.031), prominence of nucleoli (P<.001), mitotic count (P<.001), and atypical mitoses (P<.001) by univariate analysis. Multivariate analysis revealed nuclear atypia (P=.012) and mitotic count (P<.001) as independent prognostic factors, and these two factors were used to create a three-tier nuclear grade score. The resulting nuclear grade stratified patients into three distinct prognostic groups: grade I (n=107; median overall survival, 28 months), grade II (n=91; 14 months), and grade III (n=34; five months). Nuclear grade was not only an independent predictor of overall survival (P<.001) but also a stronger discriminator of survival than all available factors. Furthermore, nuclear grade was associated with time to recurrence (P=.004) in patients who underwent complete surgical resection (n=159). MIB-1 labeling index correlated with mitotic count (P<.001) and nuclear atypia (P=.037) and stratified overall survival (P<.001) and time to recurrence (P=.048), confirming the prognostic value of nuclear grade. The authors concluded that nuclear grading in epithelioid mesothelioma provides a simple, practical, and cost-effective prognostic tool that better stratifies clinical outcome and time to recurrence than do available clinicopathologic factors. Kadota K, Suzuki K, Colovos C, et al. A nuclear grading system is a strong predictor of survival in epithelioid diffuse malignant pleural mesothelioma. Mod Pathol. 2012;25:260–271. Correspondence: Dr. P. S. Adusumilli at adusumip@mskcc.org
Little is known about the clinical and pathological manifestations of isolated colonic Crohn’s disease. The authors conducted a study to evaluate the clinical and pathological features of patients with Crohn’s disease limited to the colon at initial presentation and to determine whether there are histological features that are predictive of outcome after surgery. They assessed the clinical features, outcome after surgery, and pathological features of colonic resection specimens from 73 patients who presented initially with isolated colonic Crohn’s disease and compared those findings with those from 45 Crohn’s disease patients who presented initially with ileal and colonic involvement. Clinically, patients with isolated colonic Crohn’s disease presented at a significantly older age at the time of diagnosis and had a significantly shorter duration of colitis before surgical resection than did patients with ileocolonic Crohn’s disease at disease onset. Pathologically, patients with isolated Crohn’s disease showed a significantly higher proportion of cases with subtotal, total, or left-sided colitis and significantly fewer strictures/stenoses, pericolonic adhesions, cases of pyloric metaplasia, and cases with proximal worse than distal colonic disease. Overall, patients with isolated colonic Crohn’s disease showed a trend toward a lower number of major microscopic Crohn’s disease features. A small proportion of patients from both Crohn’s disease groups (14 percent and 13 percent, respectively) showed inflammatory disease limited to the mucosa, without mural involvement, reminiscent of ulcerative colitis, and these were termed ulcerative colitis-like Crohn’s disease. These patients were significantly younger than those with mural involvement. Overall, 44 percent of patients from both Crohn’s disease groups developed at least one adverse outcome, and neither the number nor the type of major Crohn’s disease features correlated with adverse outcome. The authors concluded that patients with isolated colonic involvement have distinctive clinical and pathological features. A small subgroup of Crohn’s patients shows only mucosal involvement reminiscent of ulcerative colitis. Soucy G, Wang HH, Farraye FA, et al. Clinical and pathological analysis of colonic Crohn’s disease, including a subgroup with ulcerative colitis-like features. Mod Pathol. 2012;25:295–307. Correspondence: Dr. R. D. Odze at rodze@partners.org
Venous invasion is an independent prognostic indicator of recurrence and survival in colorectal cancer. The guidelines of the Royal College of Pathologists state that, in a series of resections, extramural venous invasion should be detected in at least 25 percent of specimens. However, there is widespread variability in the reported incidence, and this may affect patients’ access to adjuvant therapy. The authors conducted a study to clarify the practice patterns of pathologists for assessing venous invasion and to identify factors associated with an increased self-reported detection rate. They mailed a population-based survey to 361 pathologists in the province of Ontario, Canada. The overall response rate was 64.9 percent. Most of the pathologists were practicing in community-based centers (66.2 percent), and approximately half had been in practice for more than 15 years (53.5 percent). A subspecialist interest in gastrointestinal pathology was declared by 27.3 percent of the pathologists. The majority (70.2 percent) reported that they detected venous invasion in less than 10 percent of resection specimens, with only 9.1 percent reporting detection rates above 20 percent. Standardized reporting criteria were applied by 62.1 percent. Special stains were employed by 57.6 percent if venous invasion was suspected on hematoxylin and eosin-stained sections. Practice in a university-affiliated center, a subspecialist interest in gastrointestinal pathology, and acceptance of the “orphan arteriole” sign were independently associated with a self-reported venous invasion detection rate above 10 percent on multivariate analysis. The authors concluded that self-reported venous invasion detection rates are low among most pathologists. Even among specialist gastrointestinal pathologists practicing in university-affiliated centers, few reported a detection rate close to that recommended by the Royal College of Pathologists. Strategies to increase the detection of venous invasion may be required. Messenger DE, Driman DK, McLeod RS, et al. Current practice patterns among pathologists in the assessment of venous invasion in colorectal cancer. J Clin Pathol. 2011;64(11):983–989. Correspondence: Dr. Richard Kirsch at rkirsch@mtsinai.on.ca
The authors conducted a study to determine the frequency and distribution of fallopian tube involvement in patients with ovarian metastases of non-gynecological origin. All fallopian tube tissue was processed for histological examination in a consecutive series of 31 patients with ovarian metastases of non-gynecological origin. The most common primary sites were appendix (n=10), colon (n=7), stomach (n=6), and breast (n=4). Twenty cases (65 percent) showed at least one type of tubal spread. Mural involvement was most common (14 cases), but serosal, intra-vascular, intra-epithelial, and intra-luminal spread were also identified in 12, nine, eight, and 11 cases, respectively. Intra-epithelial involvement was restricted to the fimbrial epithelium and mimicked tubal carcinoma in situ (CIS) architecturally. Pagetoid invasion was noted in two of the cases. The authors concluded that the fallopian tubes are commonly involved in patients who have neoplasms metastatic to the ovaries. Metastases may show a CIS-like pattern of intra-epithelial spread. Therefore, small serous CIS-type lesions may not represent proof of tubal tumor origin in patients who have high-stage pelvic serous carcinomas. The frequency of intra-luminal tumor cells supports transtubal spread as a likely mechanism for mucosal involvement by metastatic tumors involving the lower genital tract. Stewart CJ, Leung YC, Whitehouse A. Fallopian tube metastases of non-gynaecological origin: a series of 20 cases emphasizing patterns of involvement including intra-epithelial spread. Histopathology. 2012;60(6B):E106–E114. Correspondence: Dr. C. J. Stewart at colin.stew art@health.wa.gov.au
As a putative marker for cancer stem cells in human malignant tumors, including ovarian cancer, CD133 expression may define a tumor-initiating subpopulation of cells and is associated with the clinical outcome of patients. However, its clinical significance in ovarian cancer remains uncertain. The authors conducted a study to clarify the clinical role of CD133 expression in ovarian cancer. They performed immunohistochemical staining of CD133 expression on 400 ovarian carcinoma samples using tissue microarray. The authors analyzed the associations among CD133 expression and clinical factors (diagnosis, tumor grade, cancer stage, and clinical response to chemotherapy), overall survival time, and disease-free survival time. CD133 expression was found in 31 percent of ovarian carcinoma samples. Fisher’s exact test and one-way analysis of variance suggested that CD133 expression was associated with high-grade serous carcinoma (P=.035), late-stage disease (P<.001), ascites level (P=.010), and nonresponse to chemotherapy (P=.023). CD133 expression was also associated with shorter overall survival time (P=.007) and shorter disease-free survival time (P<.001) by log-rank test. Moreover, CD133 expression was an independent predictor of shorter disease-free survival time in an unconditional logistic regression analysis with multiple covariates (P=.024). Therefore, the results show that CD133 expression is a predictor of poor clinical outcome for patients with ovarian cancer, supporting the proposed link between CD133 and cancer stem cells. Zhang J, Guo X, Chang DY, et al. CD133 expression associated with poor prognosis in ovarian cancer. Mod Pathol. 2012;25:456–464 Correspondence: Dr. J. Liu at jliu@mdanderson.org
Conventional tumor grading systems based on degree of tumor differentiation may not always be the optimal choice because of difficulty in objective assessment and insufficient prognostic value for decisionmaking in colorectal cancer treatment. The authors conducted a study to determine the importance of assessing the number of poorly differentiated clusters as the primary criterion for histologic grading of colorectal cancer. They undertook a pathological review of 500 consecutive patients with curatively resected stage II and III colorectal cancers from 2000 to 2005. Clusters of five or more cancer cells and lacking a gland-like structure were counted under a ×20 objective lens in a field containing the highest number of clusters. Tumors with fewer than five, five to nine, and 10 or more clusters were classified as grade G1, G2, and G3, respectively (n=156, 198, and 146 tumors, respectively). Five-year disease-free survival rates were 96 percent, 85 percent, and 59 percent for G1, G2, and G3, respectively (P<.0001). Poorly differentiated clusters affected survival outcome independent of T and N stages and could more effectively stratify patients by survival outcome compared with tumor staging (Akaike information criterion, 1086.7 versus 1117.0; Harrell concordance index, 0.73 versus 0.67). The poorly differentiated cluster-based grading system showed a higher weighted kappa coefficient for interobserver variability (five observers) compared with conventional grading systems (mean, 0.66 versus 0.52; range, 0.55–0.73 versus 0.39–0.68). The authors concluded that their novel histologic grading system is expected to be less subjective and more informative for prognostic prediction compared with conventional tumor grading systems and tumor-node-metastasis staging. It could be valuable in determining individualized postoperative colorectal cancer treatment. Ueno H, Kajiwara Y, Shimazaki H, et al. New criteria for histologic grading of colorectal cancer. Am J Surg Pathol. 2012;36(2):193–201. Correspondence: Dr. Hideki Ueno at ueno@ndmc.ac.jp
ARID1A is a recently identified tumor-suppressor gene that is mutated in approximately 50 percent of ovarian clear-cell carcinomas. This mutation is associated with loss of ARID1A protein expression as assessed by immunohistochemistry. The authors conducted a study to determine the timing of the loss of ARID1A protein expression during the development of ovarian clear-cell carcinoma and assess its relevance in correlation to PIK3CA gene mutations. A total of 42 clear-cell carcinoma cases with adjacent putative precursor lesions (endometriosis-associated carcinoma cases [n=28] and [clear-cell] adenofibroma-associated carcinoma cases [n=14]) were selected and subjected to immunohistochemical analysis for ARID1A protein expression and direct genomic DNA sequencing of exons 9 and 20 of the PIK3CA gene. ARID1A immunoreactivity was deficient in 17 (61 percent) of the 28 endometriosis-associated carcinomas and six (43 percent) of the 14 adenofibroma-associated carcinomas. Among the precursor lesions adjacent to the 23 ARID1A-deficient carcinomas, 86 percent of the non-atypical endometriosis (12 of 14) and 100 percent of the atypical endometriosis (14 of 14) and benign (three of three) and borderline (six of six) clear-cell adenofibroma components were found to be ARID1A deficient. In contrast, in the 19 patients with ARID1A-intact carcinomas, all of the adjacent precursor lesions retained ARID1A expression regardless of their types and cytological atypia. Analysis of 22 solitary endometrioses and 10 endometrioses distant from ARID1A-deficient carcinomas showed that all of these lesions were diffusely immunoreactive for ARID1A. Among the 42 clear-cell carcinomas, somatic mutations of the PIK3CA gene were detected in 17 (40 percent) tumors, and the majority (71 percent) of these were ARID1A-deficient carcinomas. These results suggest that loss of ARID1A protein expression occurs as a very early event in ovarian clear-cell carcinoma development, similar to the pattern of PIK3CA mutation recently reported by the authors’ group, and frequently coexists with PIK3CA gene mutations. Yamamoto S, Tsuda H, Takano M, et al. Loss of ARID1A protein expression occurs as an early event in ovarian clear-cell carcinoma development and frequently coexists with PIK3CA mutations. Mod Pathol. 2012;25:615–624. Correspondence: Dr. S. Yamamoto at dr21001@ndmc.ac.jp 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, assistant professor of pathology and laboratory medicine, University of Kentucky College of Medicine; and Thomas Cibull, MD, dermatopathologist, Evanston Hospital, NorthShore University HealthSystem, Evanston, Ill. |
