CAP TODAY Pathology/Laboratory Medicine/Laboratory Management
A clinicopathological and immunophenotypic study of secretory breast carcinoma
Secretory breast carcinoma is a rare breast cancer with indolent clinical behavior. Recent research has shown that secretory breast carcinoma belongs to the phenotypic spectrum of basal-like breast carcinomas. The authors conducted a clinicopathological and immunophenotypic analysis of secretory breast carcinomas from 15 Chinese patients. The patient group consisted of two males and 13 females, who ranged in age from 10 to 67 years (median, 36 years). All patients presented with a painless and firm mass. Tumor size ranged from 10 to 55 mm. Most tumors were located in the outer upper quadrant of the breast. Two of 13 patients (15 percent) displayed positive axillary lymph nodes. At the microscopic level, the presence of intracellular and extracellular secretory material was the most remarkable feature. Most cases showed mild dysplasia cytologically. All cases were negative for estrogen receptor, progesterone receptor, and HER2. The expression rate of the basal-like marker (CK5/6 or epidermal growth factor receptor) was 87 percent (13 of 15). The basal-like phenotype was identified in 13 cases (87 percent). Followup time ranged from 10 to 55 months (median, 19 months). None of the cases had evidence of recurrence and metastasis. This study revealed that secretory breast carcinoma is a distinct subset of invasive breast carcinoma, with expression of basal-like markers. Furthermore, secretory breast carcinoma is different from conventional basal-like breast carcinomas. Additional studies are required to further understand the prognostic significance of expression of basal-like markers in secretory breast carcinoma.
Li D, Xiao X, Yang W, et al. Secretory breast carcinoma: a clinicopathological and immunophenotypic study of 15 cases with a review of the literature. Mod Pathol. 2012;25:567–575.
Correspondence: Dr. W. Yang at ywentao2000@yahoo.com
Twenty-year survival among a population diagnosed with thin melanoma
The 20-year survival rates are unknown for the majority of melanoma patients—those with thin melanomas. The authors determined the 20-year survival rates for patients diagnosed with thin melanomas (1.00 mm or less) in the general population of Queensland, Australia. They also determined the main prognostic factors. Available clinical and histological data from the Queensland Cancer Registry were obtained for all patients diagnosed with a single thin invasive melanoma from 1982 to 2006 and matched against national death registration data. Melanoma-specific survival estimates to Dec. 31, 2007 were assessed, and subgroup differences in prognosis were determined by fitting multivariate Cox proportional hazard models. Among 26,736 people in the state of Queensland diagnosed with thin melanomas, the 20-year survival rate was 96 percent. The most influential determinants of prognosis were tumor thickness of 0.75 mm or greater (adjusted hazard ratio [HR], 4.33; 95 percent confidence interval [CI], 2.8–6.8 compared with tumors of less than 0.25 mm) and patient age at diagnosis older than 65 years (HR, 2.8; 95 percent CI, 1.8–4.5) compared with age younger than 25 years. Acral lentiginous and nodal tumors, male gender, tumor site on the scalp or neck, or tumor invasion of the entire papillary dermis each independently increased the risk of dying from thin invasive melanoma. The authors concluded that the outlook for patients with thin invasive melanoma is positive, although continued clinical vigilance is warranted for patients with nodular melanoma and those with the thickest tumors.
Green AC, Baade P, Coory M, et al. Population-based 20-year survival among people diagnosed with thin melanomas in Queensland, Australia. J Clin Oncol. 2012;30(13):1462–1467.
Correspondence: Dr. Adéle C. Green at adele.green@qimr.edu.au
Molecular basis of EPCAM expression loss in Lynch syndrome-associated tumors
Germline deletions affecting the epithelial cell adhesion molecule (EPCAM) gene lead to silencing of MSH2 and cause Lynch syndrome. The authors recently reported that lack of EPCAM expression occurs in many, but not all, tumors from Lynch syndrome patients with EPCAM germline deletions. The differences in EPCAM expression were not related to localization of EPCAM germline deletions. The authors, therefore, hypothesized that the type of the second somatic hit, which leads to MSH2 inactivation during tumor development, determines EPCAM expression in the tumor cells. To test this hypothesis and evaluate whether lack of EPCAM expression can already be detected in Lynch syndrome-associated adenomas, the authors analyzed four carcinomas and two adenomas from EPCAM germline deletion carriers for EPCAM protein expression and allelic deletion status of the EPCAM gene region by multiplex ligation-dependent probe amplification. In four of six tumors, the authors observed lack of EPCAM expression accompanied by biallelic deletions affecting the EPCAM gene. In contrast, monoallelic retention of the EPCAM gene was observed in the remaining two tumors with retained EPCAM protein expression. These results demonstrate that EPCAM expression in tumors from EPCAM deletion carriers depends on localization of the second somatic hit that inactivates MSH2. Moreover, the authors reported lack of EPCAM protein expression in a colorectal adenoma, suggesting that EPCAM immunohistochemistry may detect EPCAM germline deletions already at a precancerous stage.
Huth C, Kloor M, Voigt AY, et al. The molecular basis of EPCAM expression loss in Lynch syndrome-associated tumors. Mod Pathol. 2012;25:911–916.
Correspondence: Dr. M. Kloor at matthias.kloor@med.uni-heidelberg.de
Image and statistical analysis of melanocytic histology
The authors applied digital image-analysis techniques to study selected types of melanocytic lesions. They used advanced digital image-analysis to compare melanocytic lesions as follows: melanoma to nevi, melanoma subtypes to nevi, severely dysplastic nevi to other nevi, and melanoma to severely dysplastic nevi. The authors were successful in differentiating melanoma from nevi (receiver operating characteristics [ROC] area, 0.95) using image-derived features, among which those related to nuclear size and shape and distance between nuclei were most important. By dividing melanoma into subtypes, even greater separation was obtained (ROC area, 0.98 for superficial spreading melanoma; 0.95 for lentigo maligna melanoma; 0.99 for unclassified). Severely dysplastic nevi were best differentiated from conventional and mildly dysplastic nevi by differences in cellular staining qualities (ROC area, 0.84). The authors found that melanomas were separated from severely dysplastic nevi by features related to shape and staining qualities (ROC area, 0.95). All comparisons were statistically significant (P<.0001). The authors concluded that they offered a unique perspective into the evaluation of melanocytic lesions and demonstrated a technological application that has potential use as an adjunct to traditional diagnosis in the future.
Miedema J, Marron JS, Niethammer M, et al. Image and statistical analysis of melanocytic histology. Histopathology. 2012;61:436–444.
Correspondence: Dr. N. E. Thomas at nancy_thomas@med.unc.edu