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  Anatomic Abstracts





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July 2005

Michael Cibull, MD
Subodh Lele, MD
Melissa Kesler, MD

Deep-seated, well-differentiated lipomatous tumors of the chest wall and extremities
Breast conservation after neoadjuvant chemotherapy: a prognostic index
False-positive diagnoses of fine-needle aspiration of pulmonary hamartoma
Gastrointestinal stromal tumors of the stomach
Protein expression and diagnosis of thyroid tumors

Deep-seated, well-differentiated lipomatous tumors of the chest wall and extremities

Intramuscular lipomas and atypical lipomatous tumors are common deep-seated lipomatous tumors of the chest wall and extremities. It can be difficult to distinguish between these two entities using only histologic analysis. However, the cytogenetic profiles of ALT and intramuscular lipomas are distinct. Correct classification is important because aggressive local disease recurrence occurs more frequently in patients with ALT than in patients with intramuscular lipomas. For this study, the authors examined their single institutional experience and correlated their classification with clinical features and outcome. They classified 106 patients with deep-seated, well-differentiated adipose tumors of the chest wall and extremities as having atypical lipomatous tumors or intramuscular lipomas using a combined approach of histology and cytogenetics, if available. The classification was correlated with clinicopathologic features and followup data. Fifty-five patients were classified as having intramuscular lipomas and 51 were classified as having ALT. Classification did not correlate with age and gender (P=0.28 and P=0.96, respectively). Intramuscular lipomas were smaller than ALTs (P<0.0001), but there was significant overlap between the two groups. ALT occurred preferentially in the lower extremity (P<0.0009). Four percent of patients with intramuscular lipomas and 27 percent of patients with ALTs developed local disease recurrence (P=0.0006). Disease recurrence did not correlate with patient age at diagnosis, patient gender, tumor size, or tumor location (P=0.45, P=0.26, P=0.49, and P=0.28, respectively). Within the subset of patients with ALTs, disease recurrence did not correlate with patient age at diagnosis, patient gender, or tumor location (P=0.38, P=0.54, and P=0.86, respectively). The authors concluded that classification of deep-seated, well-differentiated lipomatous tumors of the extremities and chest wall using a combined approach of histology and cytogenetics correlated well with biologic behavior/disease recurrence. This combined approach is advocated to better stratify patients for treatment purposes and follow-up.

Bassett MD, Schuetze SM, Disteche C, et al. Deep-seated, well differentiated lipomatous tumors of the chest wall and extremities: the role of cytogenetics in classification and prognostication. Cancer.


Reprints: Dr. Brian P. Rubin, Dept. of Anatomic Pathology, University of Washington Medical Center, 1959 N.E. Pacific St., P.O. Box 356100, Seattle, WA 98195;

Breast conservation after neoadjuvant chemotherapy: a prognostic index

The appropriate selection criteria for breast-conserving therapy after neoadjuvant chemotherapy are poorly defined. The authors developed a prognostic index to help refine selection criteria and to serve as a general framework for clinical decisionmaking for patients treated by this multimodality approach. From a group of 340 patients treated with breast-conserving therapy after neoadjuvant chemotherapy, the authors previously determined four statistically significant predictors of ipsilateral breast tumor recurrence (IBTR) and locoregional recurrence (LRR): clinical N2 or N3 disease, residual pathologic tumor size greater than 2 cm, multifocal pattern of residual disease, and lymphovascular space invasion in the specimen. The M.D. Anderson Prognostic Index (MDAPI) was developed by assigning scores of zero (favorable) or one (unfavorable) for each of these four variables and using the total to give an overall MDAPI score of zero to four. The authors found that the MDAPI stratified the 340 patients into three subsets with statistically different levels of risk for IBTR and LRR after neoadjuvant chemotherapy and breast-conserving therapy. Actuarial five-year IBTR-free survival rates were 95 percent, 88 percent, and 82 percent for patients in the low (MDAPI overall score, zero or one, n=276), intermediate (MDAPI score, two, n=43), and high (MDAPI score, three or four, n=12) risk groups, respectively (P<0.001). Corresponding actuarial five-year LRR-free survival rates were 94 percent, 83 percent, and 58 percent, respectively (P<0.001). The authors concluded that patients with an MDAPI score of zero or one, which made up 81 percent of the study population, had very low rates of IBTR and LRR. Using the MDAPI, the authors were able to identify a small group (four percent) of patients who are at high risk for IBTR and LRR and who may benefit from alternative locoregional treatment strategies.

Chen AM, Meric-Bernstam F, Hunt KK, et al. Breast conservation after neoadjuvant chemotherapy: a prognostic index for clinical decision-making. Cancer. 2005;103:689-695.

Reprints: Dr. Thomas A. Buchholz, Dept. of Radiation Oncology, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd., Unit 97, Houston, TX 77030;

False-positive diagnoses of fine-needle aspiration of pulmonary hamartoma

The authors used data from the College of American Pathologists Interlaboratory Comparison Program in Nongynecologic Cytology to determine the accuracy of fine-needle aspiration biopsy for identifying lesions and determining potential sources of interpretative errors for pulmonary hamartoma. The study consisted of a retrospective review of the CAP’s nongynecologic cytology cumulative data from 1997 to 2003 to identify the overall accuracy of fine-needle aspiration (FNA) for diagnosing pulmonary hamartoma and to determine the most common interpretative pitfalls. The slides from each of the cases of pulmonary hamartoma in the nongynecologic cytology program were then reviewed to identify the cytologic characteristics that contributed to the poor performance of these cases. A total of 766 participant responses for 19 pulmonary hamartoma FNA specimens were reviewed. The specificity of FNA for making the correct general reference interpretation of benign was 78 percent. The false-positive rate was 22 percent, with the most common false-positive diagnoses being carcinoid tumor, adenocarcinoma, and small-cell carcinoma. The overall accuracy for making the correct specific reference diagnosis of pulmonary hamartoma was 26 percent. Microscopic review of the individual cases revealed possible explanations for some of the interpretative errors and the most frequent false-positive interpretations. The authors concluded that cytologists should be aware of the potential false-positive interpretations that can occur in FNAs of pulmonary hamartoma and the potential reasons for these inaccuracies in order to reduce the number of clinically significant diagnostic errors.

Hughes JH, Young NA, Wilbur DC, et al. Fine-needle aspiration of pulmonary hamartoma: a common source of false-positive diagnoses in the College of American Pathologists Interlaboratory Comparison Program in Nongynecologic Cytology. Arch Pathol Lab Med. 2005;129:19-22.

Reprints: Dr. Jonathan H. Hughes, Laboratory Medicine Consultants Ltd., 3059 S. Maryland Parkway, #100, Las Vegas, NV 89109-2201;

Gastrointestinal stromal tumors of the stomach

Gastrointestinal stromal tumors, the specific KIT- or PDFGRA-signaling driven mesenchymal tumors, are the most common mesenchymal tumors of the GI tract. In this study, the authors analyzed 1,869 cases originally classified as smooth muscle tumors of the stomach and found that 1,765 (94 percent) of these were gastrointestinal stromal tumors. The GISTs were slightly more predominant in men (55 percent). Only 2.7 percent of tumors occurred in subjects before the age of 21 years and 9.1 percent before the age of 40 years (median age, 63 years). The tumors varied from 0.5 cm to 44 cm (median, 6.0 cm) and most patients commonly presented with GI bleeding; 12 percent were incidentally detected. Several histologic variants were recognized among the spindle cell tumors (sclerosing, palisaded-vacuolated, hypercellular, and sarcomatous) and epithelioid tumors (sclerosing, dyscohesive, hypercellular, and sarcomatous). Outcome was strongly dependent on tumor size and mitotic activity. Only two percent to three percent of tumors less than 10 cm and less than five mitoses/50 HPFs metastasized, whereas 86 percent of tumors greater than 10 cm and greater than 5 mitoses/50 HPFs metastasized. However, tumors greater than 10 cm with mitotic activity less than 5/50 HPFs and those less than 5 cm with mitoses greater than 50 HPFs had a relatively low metastatic rate (11 percent and 15 percent). A small number of patients survived intra-abdominal metastasis for up to more than 20 years. Tumor location in fundus or gastroesophageal junction, coagulative necrosis, ulceration, and mucosal invasion were unfavorable factors (P<0.001), whereas tumor location in antrum was favorable (P<0.001). KIT expression was detected in 91 percent of the cases, CD34 in 82 percent, smooth muscle actin in 18 percent, and desmin in five percent; the latter two were favorable (P<0.001). KIT exon 11 mutations were detected in 119 cases. Patients with point mutations fared better than those with deletions (P<0.01). PDGFRA exon 18 mutations (total, 86 cases) were common in epithelioid GISTs and most commonly represented a D842V point mutation; none of these was prognostically significant. The authors concluded that these results may be helpful for setting the criteria for adjuvant treatment such as Gleevec.

Miettinen M, Sobin LH, Lasota J. Gastrointestinal stromal tumors of the stomach: a clinicopathologic, immunohistochemical, and molecular gene study of 1765 cases with long-term follow-up. Am J Surg Pathol. 2005;29:52-68.

Reprints: Dr. Markku Miettinen, Dept. of Soft Tissue Pathology, Armed Forces Institute of Pathology, 6825 16th St. NW, Bldg. 54, Rm. G090, Washington, DC 20306-6000;

Protein expression and diagnosis of thyroid tumors

The diagnosis of thyroid tumors is critical for clinical management; however, tumors with follicular architecture often present problems. The authors evaluated the diagnostic use of the protein expression of four genes that were found to be upregulated in papillary thyroid carcinoma compared to normal thyroid—LGALS3, FN1, CITED1, and KRT19—and of the mesothelial cell surface protein recognized by monoclonal antibody HBME1 in thyroid tumors. Tissues from 85 carcinomas (67 papillary, six follicular, eight Hürthle cell, and four anaplastic) and 21 adenomas were evaluated by immunohistochemistry for the expression of these gene protein products—for example, galectin-3 (GAL3), fibronectin-1 (FN1), CITED1, cytokeratin-19 (CK19), and HBME1. Non-neoplastic thyroids (29 adenomatous, 14 thyrotoxic hyperplasia, and 59 normal) were also studied. The expression of all five proteins was significantly associated with malignancy and highly specific (90 percent or greater) for carcinoma compared to adenoma. GAL3, FN1, and/or HBME1 expression was seen in 100 percent of carcinomas and 24 percent of adenomas. Co-expression of multiple proteins was seen in 95 percent of carcinomas and only five percent of adenomas (P<0.0001). Co-expression of FN1 and GAL3 (FN1+GAL3+, 70/85) or FN1 and HBME1 (FN1+HBME1+, 53/85) was restricted to carcinomas, while their concurrent absence (FN1- Gal3- or FN1- HBME1-, 18/21 adenoma) was highly specific (96 percent) for benign lesions. Among non-neoplastic thyroids, adenomatous hyperplasia frequently expressed GAL3 (n=16), CK19 (n=9), and CITED1 (n=7), but the expression was predominantly focal in contrast to the diffuse expression in carcinomas. An immunohistochemical panel consisting of GAL3, FN1, and HBME1 may be useful in the diagnosis of follicular cell-derived thyroid tumors.

Prasad ML, Pellegata NS, Huang Y, et al. Galectin-3, fibronectin-1, CITED1, HBME1 and cytokeratin-19 immunohistochemistry is useful for the differential diagnosis of thyroid tumors. Mod Pathol. 2005;18:48-57.

Reprints: Dr. M.L. Prasad, Dept. of Pathology, Ohio State University Medical Center, E. 418 Doan Hall, 410 W. 10th Ave., Columbus, OH 43210;

Dr. Cibull is professor of pathology and laboratory medicine and direct of surgical pathology, University of Kentucky Medical Center, Lexington. Dr. Lele is assistant professor of pathology and laboratory medicine, University of Kentucky Medical Center. Dr. Kesler is hematopathology fellow, University of Texas Southwestern Medical Center at Dallas.