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  Anatomic Abstracts





May 2009

Michael Cibull, MD
Melissa Kesler, MD

Interobserver variability in assessing radical prostatectomy specimens
Classifying the spectrum of goblet cell carcinoid tumors of the appendix
Myofibroblastoma of the breast: tumor with a wide morphologic spectrum
Gastro-oesophageal reflux disease and eosinophilic oesophagitis: a comparison
Determining adequate number of samples for extraplacental membranes

Interobserver variability in assessing radical prostatectomy specimens Interobserver variability in assessing radical prostatectomy specimens

Accurate Gleason score, pathologic stage, and surgical margin are critical for planning post-radical prostatectomy management in patients with prostate cancer. Although interobserver variability among urologic pathologists for Gleason score has been well documented, data on interobserver variability for pathologic stage and surgical margin assessment are limited. The authors addressed interobserver variability among a group of expert pathologists for extraprostatic extension (EPE) and surgical margin interpretation for radical prostatectomy specimens. A panel of three urologic pathologists selected six groups of 10 slides designated as positive, negative, or equivocal for EPE or surgical margin based on unanimous agreement. Twelve expert urologic pathologists who were blinded to the panel diagnoses reviewed 40∞ whole-slide scans and provided diagnoses for EPE and surgical margin on each slide. Using panel diagnoses as the gold standard, specificity, sensitivity, and accuracy values were high for EPE (87.5 percent, 95 percent, and 91.2 percent) and surgical margin (97.5 percent, 83.3 percent, and 90.4 percent). Overall kappa values for all 60 slides were 0.74 for surgical margin and 0.63 for EPE. The kappa values were higher for slides with definitive gold standard EPE (κ=0.81) and surgical margin (κ=0.73) diagnoses when compared with the EPE (κ=0.29) and surgical margin (κ=0.62) equivocal slides. This difference was markedly pronounced for EPE. The authors concluded that urologic pathologists show good to excellent agreement when evaluating EPE and surgical margin. Interobserver variability for EPE and surgical margin interpretation was principally related to the lack of a clearly definable prostatic capsule and crush/ thermal artifact along the edge of the gland, respectively.

Evans AJ, Henry PC, Van der Kwast TH, et al. Interobserver variability between expert urologic pathologists for extraprostatic extension and surgical margin status in radical prostatectomy specimens. Am J Surg Pathol. 2008;32:1503–1512.

Correspondence: Dr. Andrew J. Evans at
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Classifying the spectrum of goblet cell carcinoid tumors of the appendix Classifying the spectrum of goblet cell carcinoid tumors of the appendix

Appendiceal tumors exhibiting neuroendocrine and glandular differentiation are uncommon. It is difficult to classify them pathologically, predict their prognosis, and manage them clinically. Such lesions previously have been designated as adenocarcinoid, goblet cell carcinoid (GCC), and mixed adenocarcinoma carcinoid. The authors undertook a retrospective investigation of 63 such cases and classified them as typical GCC (group A) and adenocarcinoma ex GCC on the basis of the histologic features of the tumor at the primary site. The adenocarcinoma ex GCC group was further divided into signet ring cell type (group B) and poorly differentiated adenocarcinoma type (group C). The clinical characteristics and prognosis were compared within these groups and with conventional de novo appendiceal adenocarcinomas. Tumors from groups A and B shared a similar immunoprofile, which included generally focal immunoreactivity for neuroendocrine markers and a normal intestinal type mucin glycoprotein profile (negative MUC1 expression and preserved MUC2 immunoreactivity). The proliferative index was relatively low in these tumors and slightly increased from group A to B tumors (11 percent to 16 percent). Both β-catenin and E-cadherin exhibited a normal membranous staining pattern in group A and B tumors. The poorly differentiated adenocarcinomas ex GCC (group C) demonstrated abnormal p53 and β-catenin immunoreactivity. The mean followup was 49±5 months. The overall disease-specific survival rate for all subtypes was 77 percent, with 46 percent of patients without evidence of disease and 31 percent alive with disease. The mean survival rate was 43±7 months. All patients with clinical stage I or IIA disease had a favorable outcome after appropriate surgery, with or without chemotherapy. Although most patients (63 percent) with GCC presented at an advanced clinical stage, their clinical outcome could be differentiated by subclassification of tumors. The stage IV-matched five-year survival rate was 100 percent, 38 percent, and zero for groups A, B, and C, respectively. The authors concluded that GCC is a distinctive appendiceal neoplasm that exhibits unique pathologic features and clinical behavior. It displays a spectrum of histologic features and possesses the potential to transform into an adenocarcinoma phenotype of signet ring cell or poorly differentiated adenocarcinoma types. Careful evaluation of the morphologic features of GCCs and appropriate pathologic classification are crucial for clinical management and to predict outcome. Surgical management with right hemicolectomy is recommended after appendectomy for most cases, particularly those with an adenocarcinoma component (groups B and C).

Tang LH, Shia J, Soslow RA, et al. Pathologic classification and clinical behavior of the spectrum of goblet cell carcinoid tumors of the appendix. Am J Surg Pathol. 2008;32:1429–1443

Correspondence: Dr. David S. Klimstra at
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Myofibroblastoma of the breast: tumor with a wide morphologic spectrum Myofibroblastoma of the breast: tumor with a wide morphologic spectrum

Myofibroblastoma of the breast is an unusual benign tumor that belongs to the family of the benign spindle cell tumors of the mammary stroma. The name myofibroblastoma (MFB) reflects its cellular composition, which is primarily stromal cells with fibromyofibroblastic and, less frequently, myoid differentiation. Since its original description, the morphologic spectrum of MFB has been expanded with the identification of several unusual morphologic variants, including cellular, infiltrative, epithelioid, deciduoid-like, lipomatous, collagenized/fibrous, and myxoid variants. The author reviewed the literature on mammary MFB specific to the primary clinical, radiologic, and pathologic features helpful for diagnosis. Because MFB may show alarming morphologic features, which can lead to a misdiagnosis of malignancy, histologic figures of this tumor, including its more unusual variants, are provided to offer pathologists a practical approach for providing a correct diagnosis. Histogenesis and pathogenesis of this tumor are also proposed. The author extracted clinicopathologic data on MFB from all identified articles through PubMed-based research. Histologic figures were taken from the author’s personal archive. The author concluded that the incidence of MFB diagnosis has increased in recent years, likely due to mammographic screening. Accordingly, this unusual benign tumor may represent a potential diagnostic pitfall, especially when interpreting fine-needle aspiration or needle core biopsy, or both. Pathologists should be aware of the wide morphologic spectrum exhibited by MFB to avoid a misdiagnosis of malignancy.

Magro G. Mammary myofibroblastoma: a tumor with a wide morphologic spectrum. Arch Pathol Lab Med. 2008;132:1813–1820.

Correspondence: Dr. Gaetano Magro at
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Gastro-oesophageal reflux disease and eosinophilic oesophagitis: a comparison Gastro-oesophageal reflux disease and eosinophilic oesophagitis: a comparison

Eosinophil infiltration of the oesophageal epithelium is the cardinal pathomorphological finding in eosinophilic oesophagitis (EO), but gastro-oesophageal reflux disease (GORD) is also associated with increased eosinophils. The authors conducted a study to compare histological parameters for the diagnosis of EO versus GORD on biopsy specimens obtained routinely. They analyzed 105 routine biopsy specimens with EO (n=62), GORD (n=24), and probable EO (n=19) from 74 patients (52 men and 22 women; mean age, 43.7 years) for numbers of eosinophils, mast cells, degranulation, and qualitative changes of oesophageal epithelium. The analysis was carried out using immunohistochemistry with monoclonal antibodies against eosinophil peroxidase and eosinophil major basic protein and mast cell tryptase. The authors found that eosinophil infiltration was significantly higher in EO than in GORD based on hematoxylinandeosin staining (54.8 versus 9.1; P<.05) and immunohistochemistry (77.5 versus 24.7; P<.05). Eosinophil degranulation was significantly more intense in EO than in GORD (1.16 versus 0.41; P<.05). Furthermore, eosinophiliacodependent secondary qualitative changes of squamous epithelium in EO generally were more extensive than those in GORD. The authors concluded that the histological differential diagnosis of EO and GORD should be based on eosinophil counts, secondary morphological changes of eosinophils, and oesophageal squamous epithelium, especially in cases suspicious of EO.

Mueller S, Neureiter D, Aigner T, et al. Comparison of histological parameters for the diagnosis of eosinophilic oesophagitis versus gastro-oesophageal reflux disease on oesophageal biopsy material. Histopathology. 2008;53:676–684.

Correspondence information not available.
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Determining adequate number of samples for extraplacental membranes Determining adequate number of samples for extraplacental membranes

It is generally accepted practice to submit one or two membrane rolls when examining placentas. The authors conducted a study to determine whether obtaining additional sections would increase diagnostic yield and, if so, to what degree. They prospectively procured a membrane roll section from each quadrant of its respective singleton placenta. These placentas were submitted for routine pathologic examination independent of this study. All study sections were randomized and assigned new numbers, thereby blinding the pathologist to the placenta of origin. The authors evaluated the incidence of acute chorionitis/chorioamnionitis (AC/A) and atherosis when one, two, three, or four slides were examined. The diagnostic yield from all possible combinations of singles, pairs, and triplets of sections was tabulated. When an additional slide identified more extensive acute inflammation than was demonstrated initially, the AC/A was upstaged. The authors found seven to 10 placentas with AC/A when exam­ining one section, 10 to 15 with AC/A when examining two sections, 16 to 18 with AC/A when examining three sections, and 19 with AC/A when examining four sections. Additional sections upstaged the AC/A diagnosis infrequently. Four of 53 placentas had atherosis based on review of all four slides. One slide identified one to three cases of atherosis. With a second and third section, the yield increased to two to four and three to four, respectively. The authors concluded that review of a single membrane roll identified, at most, 53 percent of cases of AC/A and 50 percent of cases of atherosis. Additional sections increased the yield for both diagnoses in a roughly linear manner.

Winters R, Waters BL. What is adequate sampling of extraplacental membranes? A randomized, prospective analysis. Arch Pathol Lab Med. 2008;132:1920–1923.

Correspondence: Dr. Brenda L. Waters at
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Anatomic pathology abstracts editors: Michael Cibull, MD, professor and vice chair, Department of Pathology and Laboratory Medicine, University of Kentucky College of Medicine, Lexington; Melissa Kesler, MD, and Rouzan Karabakhtsian, MD, assistant professors of pathology and laboratory medicine, University of Kentucky College of Medicine; and Megan Zhang, MD, visiting fellow, Division of Dermatopathology, University of California, San Francisco.