CAP TODAY Pathology/Laboratory Medicine/Laboratory Management
Editors: Michael Cibull, MD, professor emeritus, 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; Thomas Cibull, MD, dermatopathologist, Evanston Hospital, NorthShore University HealthSystem, Evanston, Ill.; and Rachel Stewart, DO, resident physician, Department of Pathology and Laboratory Medicine, University of Kentucky.
Safety and diagnostic accuracy of tumor biopsies in children with cancer
Napsin A as a specific marker for ovarian clear cell adenocarcinoma
Long-term follow-up of an active surveillance cohort of patients with prostate cancer
Primary sources of pelvic serous cancer in patients with endometrial intraepithelial carcinoma
Re-evaluating the role of sentinel lymph node biopsy in microinvasive breast carcinoma
Molecular analyses of six types of uterine smooth muscle tumors
Safety and diagnostic accuracy of tumor biopsies in children with cancer
Tumor biopsies are central to the diagnosis and management of cancer and are critical to efforts in personalized medicine and targeted therapeutics. The authors conducted a study to evaluate the safety and accuracy of biopsies in children with cancer. They reviewed, retrospectively, all biopsies performed in children at the study institution who had a suspected or established diagnosis of cancer from 2003 through 2012. Patient characteristics and disease-related and procedure-related factors were correlated with procedure-related complications and diagnostic accuracy using logistic regression analysis. A total of 1,073 biopsies were performed in 808 patients. Of 1,025 biopsies with adequate follow-up, 79 (7.7 percent) were associated with an adverse event, 35 (3.4 percent) of which were minor (grade 1-2) and 32 (3.1 percent) of which were major (grade 3-4). Grading was performed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.0). The most common major adverse events were blood transfusion (more than 10 mL/kg; 24 cases) and infection requiring intravenous antibiotics (six cases). Eleven (1.4 percent) deaths occurred within 30 days after the procedure, but the procedure may have contributed to the outcome in only two cases. A total of 926 (90.3 percent) biopsies provided definitive histologic diagnoses. Using multivariable analysis, the factors of biopsy site, preprocedure hematocrit level, and body mass index were found to be associated with the risk of postprocedural complications (P<0.0001, P<0.0001, and P=0.0029, respectively). Excisional biopsy and biopsy site were found to be independently associated with obtaining a diagnostic result (P=0.0002 and P=0.0008, respectively). The authors concluded that tumor biopsies in children with cancer are associated with a low incidence of complications and a high rate of diagnostic accuracy. The predictive factors identified for adverse outcomes may aid in risk assessment and preprocedural counseling.
Interiano RB, Loh AH, Hinkle N, et al. Safety and diagnostic accuracy of tumor biopsies in children with cancer. Cancer. 2015;121:1098–1107
Correspondence: Dr. Andrew M. Davidoff at andrew.davidoff@stjude.org
Napsin A as a specific marker for ovarian clear cell adenocarcinoma
Ovarian clear cell adenocarcinoma has a relatively poor prognosis, among the ovarian cancer subtypes, because of its high chemoresistance. The differential diagnosis of clear cell adenocarcinoma is important with regard to treatment. Napsin A is a diagnostic marker for lung adenocarcinoma, and expression of napsin A is reported in some thyroid and renal carcinomas. The authors conducted a study of napsin A expression in ovarian surface epithelial tumors. In the study, immunohistochemical analysis revealed that in 71 of 86 (83 percent) ovarian clear cell adenocarcinoma patients and all 13 patients with ovarian clear cell adenofibroma, positive napsin A staining was evident. No expression was observed in 30 serous adenocarcinomas, 11 serous adenomas or borderline tumors, 19 endometrioid adenocarcinomas, 22 mucinous adenomas or borderline tumors, 10 mucinous adenocarcinomas, and three yolk sac tumors of the ovary. Furthermore, expression of napsin A was not observed in the normal surface epithelium of the ovary, epithelia of the fallopian tubes, squamous epithelium, endocervical epithelium, or endometrium of the uterus. Therefore, the authors propose that napsin A is another sensitive and specific marker for distinguishing ovarian clear cell tumors, especially adenocarcinomas, from other ovarian tumors.
Yamashita Y, Nagasaka T, Naiki-Ito A, et al. Napsin A is a specific marker for ovarian clear cell adenocarcinoma. Mod Pathol. 2015;28:111–117.
Correspondence: Dr. Y. Yamashita at k46581a@nucc.cc.nagoya-u.ac.jp
Long-term follow-up of an active surveillance cohort of patients with prostate cancer
Active surveillance is increasingly accepted as a treatment option for favorable-risk prostate cancer. Long-term follow-up has been lacking. The authors conducted a study in which they reported the long-term outcome of a large active surveillance protocol in men with favorable-risk prostate cancer. In a prospective single-arm cohort study carried out at a single academic health sciences center, 993 men with favorable- or intermediate-risk prostate cancer were managed with an initial expectant approach. Intervention was offered for a PSA doubling time of less than three years, Gleason score progression, or unequivocal clinical progression. Main outcome measures were overall and disease-specific survival, rate of treatment, and PSA failure rate in the treated patients. Among the 819 survivors, the median follow-up time from the first biopsy was 6.4 years (range, 0.2–19.8 years). A total of 149 of 993 (15 percent) patients died, and 844 (censored rate, 85 percent) patients were alive. There were 15 (1.5 percent) deaths from prostate cancer. The 10- and 15-year actuarial cause-specific survival rates were 98.1 percent and 94.8 percent, respectively. An additional 13 (1.3 percent) patients developed metastatic disease and were alive with confirmed metastases (n=9) or died of other causes (n=4). At five, 10, and 15 years, 75.7 percent, 63.5 percent, and 55 percent of patients, respectively, remained untreated and on surveillance. The cumulative hazard ratio for nonprostate-to-prostate cancer mortality was 9.2:1. The authors concluded that active surveillance for favorable-risk prostate cancer is feasible and seems safe in the 15-year time frame. In the authors’ cohort, 2.8 percent of patients developed metastatic disease and 1.5 percent died of prostate cancer. The mortality rate is consistent with expected mortality in favorable-risk patients managed with initial definitive intervention.
Klotz L, Vesprini D, Sethukavian P, et al. Long-term follow-up of a large active surveillance cohort of patients with prostate cancer. J Clin Oncol. 2015;33;272–277.
Correspondence: Dr. Laurence Klotz at laurence.klotz@sunnybrook.ca
Primary sources of pelvic serous cancer in patients with endometrial intraepithelial carcinoma
Serous endometrial intraepithelial carcinoma is often associated with extrauterine disease. It is not clear where the extrauterine disease originates. The authors conducted a study to address this issue. They studied 135 samples from 21 serous endometrial intraepithelial carcinoma patients. They determined cellular lineage relationships between intrauterine and extrauterine serous carcinomas using TP53-mutation analysis and correlated them to the clinicopathologic features. Three conditions were found to contribute to extrauterine disease: metastasis from serous endometrial intraepithelial carcinoma (n=10) that showed identical TP53 mutation between intrauterine lesions and extrauterine disease, cases of adnexal origin (n=5) that had discordant TP53 mutations, and mixed cellular origin cases (n=6) with both identical and discordant mutation status. Patients with extrauterine disease from serous endometrial intraepithelial carcinoma metastasis typically had small tumor masses (less than 2 cm) in extrauterine sites and without a finding of serous tubal intraepithelial carcinoma, while extrauterine disease with adnexal or tubal origin commonly had larger tumor masses in extrauterine sites, including ovary and omentum, and serous tubal intraepithelial carcinoma. The majority of extrauterine diseases associated with serous endometrial intraepithelial carcinoma are metastasized from the endometrium. Serous endometrial intraepithelial carcinoma is frequently associated with serous cancers of adnexal or tubal origin, indicating that endometrial and adnexal or tubal serous cancers may share similar etiologies. TP53-mutation analysis provides a strong linkage for cellular lineage analysis. Tumor size in extrauterine disease and presence or lack of serous tubal intraepithelial carcinoma are useful clinicopathologic features to determine primary cancer site, which aids clinical management.
Jia L, Yuan Z, Wang Y, et al. Primary sources of pelvic serous cancer in patients with endometrial intraepithelial carcinoma. Mod Pathol. 2015;28:118–127.
Correspondence: Dr. W. Zheng at zhengw@email.arizona.edu
Re-evaluating the role of sentinel lymph node biopsy in microinvasive breast carcinoma
The role of sentinel lymph node biopsy in microinvasive breast carcinoma is unclear. The authors examined the incidence of lymph node metastasis in patients with microinvasive carcinoma who underwent surgery at their institution. They retrospectively reviewed their pathology database from 1994 to 2012. Of 7,000 patients surgically treated for invasive breast carcinoma, 99 (one percent) were classified as microinvasive carcinoma. Axillary staging was performed in 81 patients (64 sentinel lymph node biopsy; 17 axillary lymph node excision). Seven (nine percent) cases showed isolated tumor/epithelial cells in sentinel nodes. Three of the seven cases showed reactive changes in lymph nodes, papillary lesions in the breast with or without displaced epithelial cells within the biopsy site tract, or immunohistochemical (estrogen receptor, progesterone receptor, and HER2) discordance between the primary tumor in the breast and epithelial cells in the lymph node, consistent with iatrogenically transported epithelial cells rather than true metastasis. Among the remaining four cases were two cases with a single cytokeratin-positive cell in the subcapsular sinus detected by immunohistochemistry only and two cases with isolated tumor cells singly and in small clusters (fewer than 20 cells per cross-section) detected by hematoxylin and eosin and immunohistochemistry. The exact nature of cytokeratin-positive cells in the former two cases could not be determined and might have represented iatrogenically displaced cells. In the final analysis, only two (three percent) cases had isolated tumor cells. Three of the four cases had additional axillary lymph nodes excised, which were negative for tumor cells. At a median follow-up of 37 months (range, 6–199 months), none of these patients had axillary recurrences. The authors’ results show very low incidence of sentinel lymph node involvement (three percent), and only as isolated tumor cells, in microinvasive carcinoma patients. None of the cases showed micrometastasis or macrometastasis. The authors recommended reassessing the routine practice of sentinel lymph node biopsy in patients with microinvasive carcinoma.
Hanna MG, Jaffer S, Bleiweiss IJ, et al. Re-evaluating the role of sentinel lymph node biopsy in microinvasive breast carcinoma. Mod Pathol. 2014;27:1489–1498.
Correspondence: Dr. A. Nayak at anupma.nayak@mssm.edu
Molecular analyses of six types of uterine smooth muscle tumors
Uterine smooth muscle tumors constitute a group of histologic, genetic, and clinical heterogeneous tumors that include at least six major histologically defined tumor types: leiomyoma, mitotically active leiomyoma (MALM), cellular leiomyoma, atypical leiomyoma, uncertain malignant potential (STUMP), and leiomyosarcoma. Apart from leiomyoma and leiomyosarcoma, the nature of these variants is not well defined. For the study, 167 cases of uterine smooth muscle tumor variants were collected, reviewed, and diagnostically confirmed based on the World Health Organization and Stanford schemes. These included 38 cases of leiomyosarcoma, 18 cases of STUMP, 42 cases of atypical leiomyoma, 22 cases of cellular leiomyoma, seven cases of MALM, and 40 cases of leiomyoma. Molecular analysis included selected microRNAs, oncogenes, and tumor suppressors that are highly relevant to uterine smooth muscle tumors. Overall, 49 percent (17 of 35) of the study subjects with leiomyosarcoma and seven percent (one of 14) with STUMP died due to their uterine smooth muscle tumors, but no deaths were attributed to atypical leiomyosarcoma. MicroRNA profiling revealed that atypical leiomyosarcoma and leiomyosarcoma share similar microRNA signatures. P53 mutations and PTEN deletions were significantly higher in leiomyosarcoma, atypical leiomyosarcoma, and STUMP compared with other uterine smooth muscle tumor variants (P<0.01). In contrast, MED12 mutations were extremely common (greater than 74 percent) in leiomyoma and MALM but were significantly less common (less than 15 percent) in cellular leiomyoma, atypical leiomyoma, STUMP, and leiomyosarcoma (P<0.01). The authors concluded that the six types of uterine smooth muscle tumors studied have different gene mutation fingerprints. Atypical leiomyoma shares many molecular alterations with leiomyosarcoma. The findings suggest that atypical leiomyoma may be a precursor lesion of leiomyosarcoma or undergo similar genetic changes during its early stage.
Zhang Q, Ubago J, Li L, et al. Molecular analyses of 6 different types of uterine smooth muscle tumors: emphasis in atypical leiomyoma. Cancer. 2014;120:3165–3177.
Correspondence: Beihua Kong at kongbeihua@sdu.edu.cn or Jian-Jun Wei at jianjun-wei@northwestern.edu