Anatomic Abstracts
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July 2008 Editor:
Features of ductal carcinoma in situ associated with flat epithelial atypia
Flat epithelial atypia is an alteration of mammary terminal duct lobular units that is considered to be a precursor to, or early stage in, the development of some forms of ductal carcinoma in situ. Understanding the relationship between various clinicopathologic features of ductal carcinoma in situ and the presence of co-existent flat epithelial atypia could provide insight into the connection between flat epithelial atypia and ductal carcinoma in situ. The authors reviewed slides from 543 ductal carcinoma in situ patients enrolled in a case-control study that assessed epidemiologic and pathologic risk factors for local recurrence. They examined the association between flat epithelial atypia and various clinical factors, pathologic features of the ductal carcinoma in situ, and the presence of co-existent atypical ductal hyperplasia, lobular neoplasia, and non-atypical columnar cell lesions. In univariate analysis, flat epithelial atypia was significantly related to ductal carcinoma in situ nuclear grade (most common in low grade, least common in high grade; P<.0001), architectural pattern (most common in micropapillary and cribriform, least common in comedo; P<.0001), absence of comedo necrosis (P<.001), absence of stromal desmoplasia (P=.02), and absence of stromal inflammation (P=.03). In multivariate analysis, features of ductal carcinoma in situ independently associated with flat epithelial atypia were micropapillary and cribriform patterns and absence of comedo necrosis. Additionally, flat epithelial atypia was significantly associated with atypical ductal hyperplasia, lobular neoplasia, and columnar cell lesions in univariate and multivariate analyses. These observations provide support for a precursor-product relationship between flat epithelial atypia and ductal carcinoma in situ lesions that exhibit particular features, such as micropapillary and cribriform patterns and absence of comedo necrosis. Collins LC, Achacoso NA, Nekhlyudov L, et al. Clinical and pathologic features of ductal carcinoma in situ associated with the presence of flat epithelial atypia: an analysis of 543 patients. Mod Pathol. 2007; 20: 1149– 1155. Reprints: Dr. L. C. Collins, Dept. of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Ave., Boston, MA 02215; lcollins@bidmc.harvard.edu
Primary salivary-type lung cancers are rare tumors that include adenoid cystic carcinoma (ACC) and mucoepidermoid carcinoma (MEC). The clinicopathologic profiles, symptoms on presentation, and long-term outcomes of patients with ACC and MEC as an overall group have not been defined recently. The authors conducted a study in which they analyzed clinical outcome data from 62 patients who presented with a diagnosis of primary salivary-type lung cancer at the Mayo Clinic from 1972 to 2002. The median age at diagnosis for patients with MEC was 40 years (range, 6–78 years); and the median age at diagnosis for patients with ACC was 54 years (range, 21–76 years). ACC was observed more frequently among women and girls. The main presenting symptom for both tumors was cough (70%), followed by dyspnea (51.7%), wheezing (38.3%), obstructive pneumonia (30%), hemoptysis (28.3%), and fever (16.7%). Tissues from all patients were available for review. Among the ACC tumors, 29 (74.4%) were cribriform, seven (17.9%) tubular, and three (7.7%) solid type. Most MEC tumors (65%) were intermediate grade (grade two), and 30 percent were low grade (grade one). Most salivary-type lung cancers presented in the trachea, carina, or a main stem bronchus (70.7%). This location was observed more often (82.5%) for ACC tumors than for MEC tumors (44.4%). Involvement of the lymph nodes was observed in 20 percent of patients and was more common among patients with ACC (30.8%). Distant metastases were observed in 30.4 percent of the patients (15 patients in the ACC group [40.5%] compared with only two patients in the MEC group [10.5%]; P=.03). For patients who underwent complete surgical resection, the three-, five-, and 10-year survival rates were 82 percent, 70 percent, and 63 percent, respectively. The survival rates for surgical MEC patients were 94 percent at three years and 87 percent at five and 10 years. For surgical ACC patients, the survival rates were 73 percent, 57 percent, and 45 percent at three, five, and 10 years, respectively. The survival rates for patients with ACC who did not undergo surgery were 74 percent at three years, 53 percent at five years, and 31 percent at 10 years. The difference in survival rates between surgical and nonsurgical patients was statistically significant (P<.01). The authors concluded that patients with MEC and ACC frequently have a good long-term prognosis but do not always have indolent diseases. Local recurrence is likely if complete surgical recision is not achieved. ACC has a higher likelihood than MEC to metastasize. Overall, patients with MEC have a higher survival rate than patients with ACC. Molina JR, Aubry MC, Lewis JE, et al. Primary salivary gland-type lung cancer: spectrum of clinical presentation, histopathologic and prognostic factors. Cancer. 2007; 110: 2253–2259. Reprints: Dr. Julian R. Molina, Division of Medical Oncology, Mayo Clinic College of Medicine, 200 First St., SW, Rochester, MN 55905; molina.julian@mayo.edu
Age younger than 50 years at the time of colon cancer diagnosis is often used as a screening criterion for Lynch syndrome (hereditary nonpolyposis colorectal cancer syndrome). The authors conducted a study to determine the prevalence of MLH1, MSH2, and MSH6 mutations in an unselected cohort of women diagnosed with endometrial cancer before age 50. They performed a prospective, multicenter study at three institutions. After written consent was obtained, germline mutation testing by full sequencing and large deletion analysis of the MLH1, MSH2, and MSH6 genes were performed. Tumor studies included immunohistochemistry of MLH1, MSH2, and MSH6; microsatellite instability analysis; and hypermethylation of the MLH1 promoter. Of the 100 women, nine (9%) (95% confidence interval, 4.2–16.4) carried a deleterious germline mutation: seven women with mutations in MSH2, one with a mutation in MLH1, and one with a mutation in MSH6. Two additional women had molecular studies consistent with the diagnosis of Lynch syndrome. The mean body mass index for the entire cohort was 34.4, which is significantly higher than 29.2, the mean body mass index for the mutation carriers. Predictors of finding a germline mutation included having a first-degree relative with a Lynch syndrome-associated cancer, endometrial tumor with loss of MSH2 expression, tumors with high microsatellite instability, and lower body mass index. The authors concluded that in this prospective study of endometrial cancer patients younger than 50 years, nine percent were found to carry germline Lynch syndrome-associated mutations. In addition to young age at onset, family history, body mass index, and molecular tumor studies can improve the likelihood of identifying a Lynch syndrome-associated germline mutation in MLH1, MSH2, and MSH6. Lu KH, Schorge JO, Radabaugh KJ, et al. Prospective determination of prevalence of Lynch syndrome in young women with endometrial cancer. J Clin Oncol. 2007; 25: 5158– 5164. Reprints: Dr. Karen H. Lu, Dept. of Gynecologic Oncology, Division of Surgery, University of Texas M.D. Anderson Cancer Center, 1155 Herman Pressler, Unit 1362, Houston, TX 77030-4009; khlu@mdanderson.org
Immunohistochemistry plays a crucial role in diagnosing hepatocellular carcinoma and in distinguishing it from other primary and metastatic neoplasms. Because limited tissue is available with fine-needle and core biopsies, it is imperative to select the appropriate antibodies. The authors conducted a study to review the antibodies used for diagnosing hepatocellular carcinoma and to outline an immunohistochemical approach in commonly encountered clinical situations. To aid in their assessment, the authors used their past experiences and reviewed research articles published in the English literature between 1987 and 2006. The authors concluded that Hep Par 1 and polyclonal carcinoembryonic antigen are the most reliable markers for hepatocellular differentiation but that they have low sensitivity for poorly differentiated cases. Immunohistochemistry for glypican-3 shows promise for diagnosing poorly differentiated hepatocellular carcinoma and for distinguishing it from benign processes, such as hepatic adenoma. However, additional studies with a large number of cases are required before it can be used widely. The combination of Hep Par 1 and MOC-31 will allow for the diagnosis of hepatocellular carcinoma in most cases and will guide the selection of immunohistochemical markers for further workup. Kakar S, Gown AM, Goodman ZD, et al. Best practices in diagnostic immunohistochemistry: hepatocellular carcinoma versus metastatic neoplasms. Arch Pathol Lab Med. 2007;131:1648–1654. Reprints: Dr. Sanjay Kakar, Dept. of Anatomic Pathology, VA and UCSF Medical Centers, 4150 Clement St., San Francisco, CA 94121; sanjay.kakar@ucsf.edu
It is difficult to predict the biologic behavior of pancreatic endocrine tumors in the absence of metastases or invasion into adjacent organs. In 2004, the World Health Organization (WHO) proposed the following as prognostic criteria: size, angioinvasion, mitotic activity, and MIB1 proliferation index. The authors conducted a study to test, retrospectively, the predictive value of these 2004 WHO criteria and CK19, CD99, COX2, and p27 immunohistochemistry in a large series of patients with long-term followup. They reviewed the histology of 216 pancreatic endocrine tumor specimens and reclassified the tumors according to the 2004 WHO classification. The prognostic value of the WHO classification and the histopathologic criteria of necrosis and nodular fibrosis were tested in 113 patients. A tissue microarray was constructed for immunohistochemical staining. The staining results were scored quantitatively for MIB1 and semiquantitatively for CK19, COX2, p27, and CD99. The prognostic value of these markers was tested in 93 patients. The results showed that stratifying the patients into four risk groups according to the 2004 WHO classification was reliable with regard to time span to relapse and tumor-specific death. In multivariate analysis, CK19 status was shown to be independent of the WHO criteria. In contrast, the prognostic significance of COX2, p27, and CD99 could not be confirmed. The authors concluded that the 2004 WHO classification with four risk groups is very reliable for predicting disease-free survival and time span until tumor-specific death. CK19 staining is a potential additional prognostic marker independent from the WHO criteria for pancreatic endocrine tumors. Schmitt AM, Anlauf M, Rousson V, et al. WHO 2004 criteria and CK19 are reliable prognostic markers in pancreatic endocrine tumors. Am J Surg Pathol. 2007; 31: 1677– 1682. Reprints: Dr. Aurel Perren, Institute of Pathology, Klinikum rechts der Isar, Ismaningerstr. 22, D-81675 Munich, Germany; aurel.perren@freesurf.ch
The authors conducted a study in which they evaluated whether response to neoadjuvant chemotherapy was correlated with molecular classification groups in a molecular classification system. Using immunohistochemistry, the molecular classification group (luminal-A, luminal-B, HER-2 variant, HER-2 classic, and basal phenotype) was retrospectively determined in 68 breast cancer patients who received neoadjuvant treatment. A total of 28 (41.2%) carcinoma patients achieved a compete pathologic response, including two of 15 (13.3%) patients classified as having luminal-A, four of 16 (25%) classified as having luminal-B, 10 of 12 (83.3%) classified as having HER-2 classic, none of four classified as having HER-2 variant, and 12 of 21 (57.1%) classified as having basal phenotype neoplasms. The compete pathologic response rate among patients with HER-2 classic and basal neoplasms was 67 percent (22 of 33 neoplasms), compared with 17.1 percent (six of 35 neoplasms) in the non-HER-2 classic/basal combined group (P<.001). Eleven carcinomas were initially diagnosed as invasive lobular carcinomas (pleomorphic and classic), of which four were luminal-A, four luminal-B, two HER-2 classic, and one basal. On review, only three of these 11 cases remained classified as classic lobular carcinoma, all of which were classified as luminal-A, and none of these patients achieved a compete pathologic response. Four of the other eight patients achieved a compete pathologic response. The authors concluded that the molecular classification system is useful for identifying carcinoma patients who are most likely and those who are least likely to achieve a compete pathologic response. All the morphologically classic lobular carcinomas were classified as luminal-A neoplasms, which may explain the low rate of compete pathologic response reported. Goldstein NS, Decker D, Severson D, et al. Molecular classification system identifies invasive breast carcinoma patients who are most likely and those who are least likely to achieve a complete pathologic response after neoadjuvant chemotherapy. Cancer. 2007; 110: 1687– 1696. Reprints: Dr. Neal S. Goldstein, Dept. of Anatomic Pathology, William Beaumont Hospital, 3601 W. 13 Mile Rd., Royal Oak, MI 48073; ngoldstein@beaumont.edu
Uterine carcinosarcomas are aggressive neoplasms with five-year overall survival rates of less than 35 percent. They customarily are separated into types harboring heterologous or homologous mesenchymal elements, but the prognostic significance of this finding is controversial. The authors studied clinicopathologic features of possible prognostic relevance in surgical stage I uterine carcinosarcoma (CS). They performed a retrospective clinical and histopathologic review for all women diagnosed with surgical stage I uterine CS. The tumors were compared with stage I high-grade endometrial (HGEm) carcinomas for clinical outcomes. The authors identified 42 cases of surgical stage I uterine CS between January 1990 and January 2004. The disease-free survival and overall survival rates for patients with stage I CS were significantly worse than those for stage I HGEm (P=.001; P=.01). The median disease-free survival rate for patients with heterologous CS was 15 months and had not been reached for women with homologous CS (P=.001). The three-year overall survival rates were 45 percent versus 93 percent in women with heterologous compared with homologous stage I CS (P<.001). The three-year overall survival rates for homologous CS and those for HGEm were both greater than 90 percent. Homologous stage I CS has survival outcomes that are similar to those for HGEm. This further supports the concept that homologous stage I CSs are carcinomas with sarcomatoid features, not sarcomas. More importantly, the presence of heterologous sarcomatous elements is a powerful negative prognostic factor in surgical stage I uterine CS. Ferguson SE, Tornos C, Hummer A, et al. Prognostic features of surgical stage I uterine carcinosarcoma. Am J Surg Pathol. 2007;31: 1653–1661. Reprints: Dr. Robert A. Soslow, Gynecology Service, Dept. of Surgery, Memorial Sloan-Kettering Cancer Center, 1275 York Ave., New York, NY 10021; gynbreast@mskcc.org Dr. Cibull is professor of pathology and laboratory medicine and direct of surgical pathology, University of Kentucky Medical Center, Lexington. Dr. Kesler is hematopathology fellow, University of Texas Southwestern Medical Center at Dallas. |
