Malignant pleural mesothelioma is a refractory tumor associated with asbestos exposure and with a poor prognosis. Pleural effusion is frequently observed in patients with malignant pleural mesothelioma, and cytological analysis is effective for detecting malignant pleural mesothelioma. However, cytological discrimination between malignant pleural mesothelioma and reactive mesothelium is often difficult. Increased expression of the cell adhesion molecule CD146 has been reported to be closely associated with an advanced stage of malignant melanoma, prostate cancer, and ovarian cancer. The authors conducted a study to evaluate the diagnostic utility of CD146 for discriminating between malignant pleural mesothelioma and reactive mesothelium. They examined immunocytochemical expression of CD146 in malignant pleural mesothelioma and reactive mesothelium using two clones of CD146 antibody, OJ79 and EPR3208, on smear specimens of effusion fluids. Immunocytochemical stains were semiquantitatively scored on the basis of immunostaining intensity: zero, negative; one, weak positive; two, moderate positive; and three, strong positive. CD146 expression was detected in 15 of 16 malignant pleural mesothelioma with a median immunostaining score of three by OJ79 and in 19 of 21 malignant pleural mesothelioma with a median immunostaining score of two by EPR3208. Strong immunoreactivity of CD146 was observed at the apposing surfaces of cell-to-cell interactions on the plasma membrane of mesothelioma cells. In addition, one OJ79-negative case of malignant pleural mesothelioma was positive for CD146 by EPR3208, and two EPR3208-negative cases of malignant pleural mesothelioma were CD146 positive by OJ79, showing that all 23 malignant pleural mesothelioma cases were positive for CD146 by OJ79 or EPR3208. Yet CD146 expression was undetectable in all reactive mesothelium cases by OJ79 and EPR3208. The sensitivity of OJ79 and EPR3208 was 94 percent and 90 percent, respectively, and the specificity was 100 percent for both clones. The authors proposed that CD146 is a sensitive and specific immunocytochemical marker enabling discrimination between malignant pleural mesothelioma and reactive mesothelium.
Sato A, Torii I, Okamura Y, et al. Immunocytochemistry of CD146 is useful to discriminate between malignant pleural mesothelioma and reactive mesothelium. Mod Pathol. 2010;23:1458–1466.
Correspondence: Dr. T. Tsujimura at email@example.com
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Lung biopsies showing granulomatous disease are commonly sent for expert pathology consultation. On the basis of features the authors and others have identified, an algorithmic approach to diagnosing these cases was developed. The authors hypothesized that applying this approach would increase the likelihood of rendering a more specific diagnosis, or by rendering a narrower or broader differential diagnosis would offer a more clinically useful diagnosis. The authors retrieved from their consultation files 100 consecutive lung biopsies from patients with granulomatous and giant cell reactions. They categorized cases into those in which a confident diagnosis was made at sign out, those in which a specific diagnosis was strongly favored, and those in which a differential diagnosis was suggested. One year later, the authors obtained followup information and compared consultation diagnoses with clinical diagnoses to determine the reliability of the approach. They found that a confident diagnosis was rendered in 27 cases; a specific diagnosis was strongly favored in 34; and a differential diagnosis was provided in 39. Consultant diagnoses were more specific in 47 of 75 (63 percent) cases. In 15 cases, the differential diagnosis was expanded. The most common unrecognized diagnosis was aspiration pneumonia, and the most common diagnosis omitted from the differential diagnosis by the primary pathologist was hypersensitivity pneumonia. Followup in 49 percent of cases in which it was sought confirmed the consultant’s diagnosis or was inconclusive in 97 percent of cases. The authors concluded that the use of a standardized algorithmic approach to interpreting granulomatous disease in lung biopsies yields more specific and clinically useful diagnoses.
Hutton Klein JR, Tazelaar HD, Leslie KO, et al. One hundred consecutive granulomas in a pulmonary pathology consultation practice. Am J Surg Pathol. 2010;34(10):1456–1464.
Correspondence: Dr. H. D. Tazelaar at firstname.lastname@example.org
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Granulosa cell tumors of the ovary represent approximately five percent of malignant ovarian cancers. It recently has been reported that 95 percent to 97 percent of adult granulosa cell tumors carry a unique somatic mutation in the FOXL2 gene. The authors undertook a study to verify the presence of the FOXL2 Cys134Trp mutation in two geographically independent cohorts of granulosa cell tumors and to examine the expression pattern of FOXL2 in these tumors. They examined 56 tumors from two centers—Melbourne, Australia, and Helsinki, Finland—that had the histological diagnosis of adult granulosa cell tumor. The tumors were examined for the presence of the FOXL2 Cys134Trp mutation using direct sequence analysis. The authors also examined two granulosa cell tumor-derived cell lines, COV434 and KGN, three juvenile granulosa cell tumors, and control tissues. Expression of the FOXL2 gene was determined using quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) or immunohistochemistry, or both. The authors found that 52 of the 56 adult granulosa cell tumors harbor the FOXL2 Cyst134Trp mutation, of which three were hemi/homozygous. Of the four cases with wild-type FOXL2 sequence, reappraisal suggested that three may have been misclassified at primary diagnosis. The KGN cells were heterozygous for the mutation, whereas the COV434 cell had a wild-type FOXL2 genotype. The expression levels of FOXL2 were similar across the adult granulosa cell tumors and the normal ovary controls. One mutation-negative granulosa cell tumor had high FOXL2 mRNA levels, whereas the COV434 cells and two of the three juvenile granulosa cell tumors lacked expression of FOXL2. The authors concluded that these data confirm the frequent presence of the FOXL2 C134W mutation in adult granulosa cell tumors and demonstrate that the mutation is not associated with altered FOXL2 expression. Mutation analysis may be a useful tool to differentiate between cell-rich diffuse granulosa cell tumors and mitotically active sex cord-stromal tumors in particular. This unique FOXL2 mutation appears to be characteristic of adult granulosa cell tumors.
Jamieson S, Butzow R, Andersson N, et al. The FOXL2 C134W mutation is characteristic of adult granulosa cell tumors of the ovary. Mod Pathol. 2010;23:1477–1485.
Correspondence: Dr. M. Anttonen at email@example.com and P. J. Fuller at firstname.lastname@example.org
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Medullary carcinomas have a better prognosis than other grade three mammary carcinomas, but they typically exhibit basal-like biological features, which are associated with a poor prognosis. The authors conducted a study in which they examined the associations and prognostic relevance of medullary histological features in a series of 165 invasive carcinomas with a basal-like phenotype—triple-negative (estrogen receptor, progesterone receptor, HER2) and expressing at least one basal marker (CK5/6, CK14, CK17, or epidermal growth factor receptor). The following histological features were associated with each other: prominent inflammation, anastomosing sheets, absence of fibrosis, absence of infiltrative margin, and absence of gland formation. Prominent inflammation and anastomosing sheets in at least 30 percent of the tumor were associated with a better prognosis on univariate analysis. The combination of these two features (a simplified definition of medullary-like type) was present in 17 percent of tumors and was an independent prognostic factor on multivariate analysis. This simplified definition had good inter-observer reproducibility (k=0.61) and is worthy of more detailed assessment in an unselected group of mammary carcinomas. A fibrotic focus was present in 36 percent of carcinomas. Only three percent of tumors with a fibrotic focus had features of medullary-like carcinomas. Fibrotic focus of greater than 30 percent of the tumor was associated with a poor prognosis. The authors concluded that their study emphasizes the heterogeneity of morphology and behavior of triple-negative basal-like carcinomas.
Marginean F, Rakha EA, Ho BC, et al. Histological features of medullary carcinoma and prognosis in triple-negative basal-like carcinomas of the breast. Mod Pathol. 2010;23:1357–1363.
Correspondence: Dr. A. H. S. Lee at email@example.com
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Premalignant endometrial lesions (endometrial intraepithelial neoplasia) are clonal neoplasms that arise focally and can be diagnosed using specific criteria, including area of glands exceeds that of stroma (glands/stroma greater than one); nuclear or cytoplasmic features of epithelial cells, or both, differ between architecturally abnormal glands and normal background glands; and maximum linear dimension exceeds 1 mm. However, localized groups of crowded endometrial glands may be encountered that do not fulfill all of the criteria for endometrial intraepithelial neoplasia (EIN), are interpreted as ambiguous, and are reported as focal gland crowding. The authors conducted a retrospective study of gland crowding using a free-text index search for this term in their pathology files. They recorded the age of the patients, number of subsequent specimens, duration, and outcome of followups. From the 71,579 consecutive gynecological pathology reports, 206 (0.3 percent) “gland crowding” cases were identified, of which 69 percent (143 of 206) had followup sampling. Of these, 33 (23 percent) had an outcome diagnosis of EIN (27 cases; 19 percent) or carcinoma (six cases; four percent). Included were 18 cases (55 percent) diagnosed within the first year and presumed concurrent and an additional 15 (45 percent) discovered after one year and interpreted as a later phase of disease or new events. The term “crowded glands” is a highly significant finding that carries a substantial risk of an outcome of EIN and, occasionally, malignancy. It underscores the importance of followup when some, but not all, of the criteria for EIN are encountered in the appropriate clinical setting.
Huang EC, Mutter GL, Crum CP, et al. Clinical outcome in diagnostically ambiguous foci of ‘gland crowding’ in the endometrium. Mod Pathol. 2010;23:1486–1491.
Correspondence: Dr. M. R. Nucci at firstname.lastname@example.org
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IgG4-related disease has been identified in various organs, but whether there are organ-specific characteristics related to the etiologic factors is unknown. The authors conducted a cross-sectional study of 114 patients with IgG4-related disease. On the basis of the location of the lesions, the patients were classified into five groups: head and neck (n=23), thoracic (n=16), hepatic and pancreatobiliary (n=27), retroperitoneal (n=13), and systemic (n=35). All groups had similar clinicopathologic features in various aspects. However, there were some organ-specific features—for example, the proportion of female patients was significantly higher in the head/neck and systemic groups; and all kidney lesions were associated with extrarenal disease. Unique pathologic features were dense fibrosis in dacryoadenitis, numerous lymph follicles in sialadenitis and dacryoadenitis, and obliterative arteritis in lung lesions. In addition, an epithelioid granuloma and rheumatoid nodule were noted within IgG4-related lesions in two patients—one each with a history of tuberculosis and rheumatoid arthritis, respectively. Malignant tumors (two lung cancers and one malignant lymphoma) were identified after the diagnosis of IgG4-related disease in three patients, all of whom were in the systemic group. The authors concluded that this study showed organ-specific features of IgG4-related disease. Additional study is necessary to determine whether these features reflect different manifestations of a single disease entity or suggest different underlying etiologic factors.
Zen Y, Nakanuma Y. IgG4-related disease: a cross-sectional study of 114 cases. Am J Surg Pathol. 2010;34(12):1812–1819.
Correspondence: Dr. Yoh Zen at email@example.com
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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.