College of American Pathologists
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  Anatomic Abstracts





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September 2001

Role of E-cadherin staining in categorizing in situ carcinomas of the breast with indeterminate features
Loss of E-cadherin protein expression in invasive lobular carcinoma and lobular carcinoma in situ (LCIS) but not in invasive or in situ ductal carcinoma (DCIS) has been noted in several recent studies. In this study, the authors examined the utility of E-cadherin expression by immunohistochemistry in 89 cases of carcinoma in situ (CIS) of the breast (28 LCIS, 33 DCIS, 28 CIS with indeterminate features). The cases of CIS with indeterminate features (CIS-IF) were further divided into three groups: group one, those with cytologic and architectural features typical of LCIS with areas of comedo-type necrosis (n=6); group two, those with small uniform neoplastic cells growing in a solid pattern with focal microacinar-like structures but with cellular dyshesion (n=15) or cells growing in a cohesive mosaic pattern but with occasional intracytoplasmic vacuoles (n=2); and group three, those with marked cellular pleomorphism and nuclear atypia with the dyshesive growth pattern typical of LCIS (n=5). All 28 cases of typical LCIS were negative for E-cadherin and all 33 cases of typical DCIS were positive for E-cadherin. All cases from CIS-IF group one and group three were negative for E-cadherin. Cases from CIS-IF group two, however, were heterogeneous with respect to E-cadherin staining. The data suggest that E-cadherin immunohistochemistry is useful in categorizing carcinoma in situ of the breast with indeterminate features. The authors stated that CIS lesions with E-cadherin positivity are best considered ductal; those with E-cadherin negativity are best classified as lobular; and those with a mixed population of both positive and negative cells should be classified as combined DCIS and LCIS. Clinical outcome studies are necessary, however, to validate these findings and determine their significance.

Jacobs TW, Pliss N, Kouria G, et al. Carcinomas in situ of the breast with indeterminate features: role of E-cadherin staining in categorization. Am J Surg Pathol. 2001;25:229-236

Reprints: Timothy W. Jacobs, MD, Dept. of Pathology, Beth Israel Deaconess Medical Center, 330 Brookline Ave., Boston, MA 02215

Lymphocytic atypia as a criterion for diagnosing mycosis fungoides
The authors evaluated whether atypical lymphocytes in the epidermis or dermis, or both, are useful as diagnostic criteria for separating mycosis fungoides from benign spongiotic dermatitis. They selected hematoxylin and eosin-stained slides from 30 cases of each condition, and epidermal and dermal lymphocytes were photographed at 1,000x. The photographs were evaluated by seven expert pathologists. Atypical epidermal lymphocytes were identified in 56 percent of cases of mycosis fungoides compared with 50 percent of cases of benign spongiotic dermatitis. Similarly, atypical lymphocytes were noted in the dermis in 47 percent of the mycosis fungoides cases and 43 percent of the spongiotic dermatitis cases. Interobserver variation was broad; the seven pathologists graded lymphocytes as atypical in 25 percent to 76 percent of the study photomicrographs. Although this study is limited by the use of photographs in lieu of glass slides, the authors concluded that it is not possible to distinguish mycosis fungoides from spongiotic dermatitis solely based on lymphocytic atypia within the epidermis or dermis.

Yeh YA, Hudson AR, Prieto VG, et al. Reassessment of lymphocytic atypia in the diagnosis of mycosis fungoides. Mod Pathol. 2001;14(4):285-288.

Reprints: Dr. Bruce R. Smoller, University of Arkansas for Medical Sciences, Dept. of Pathology, 4301 West Markham St., Slot 517, Little Rock, AR 72205

Malignant fibrous histiocytomas revisited
Using material identified through a Swedish soft tissue sarcoma database, the authors re-examined the histological classification of 100 tumors previously identified as malignant fibrous histiocytoma. The tumors were from adult patients treated between 1980 and 1995. The thigh was the most common primary site, and 69 percent of the tumors were deep-seated. The tumors were reclassified using hematoxylin and eosin-stained sections for light microscopy as well as immunohistochemistry and, in a small number of cases, electron microscopy. Reclassification was correlated with tumor grade, stage, and clinical outcome. Of the 100 cases selected for study, the authors were able to reclassify 84, assigning them a specific line of differentiation. The most common diagnoses in reclassification included myxofibrosarcoma (22 cases) and leiomyosarcoma (20 cases). Overall, 30 tumors showed some form of myogenous differentiation. When correlated with outcome, myogenic tumors showed a significantly worse metastasis-free survival rate than nonmyogenic sarcomas (.39 versus .74; P<.0001). Moreover, this disadvantage persisted when only stage II and III tumors were considered. The authors concluded that those interested in diagnosing and managing patients with soft tissue sarcoma should work to minimize the use of the term malignant fibrous histiocytoma and instead concentrate on establishing a reproducible histologic subclassification of such tumors. The authors believe this will aid in developing clinical trials that address those differences in prognosis and response to therapy that reflect tumor type.

Fletcher CDM, Gustafson P, Rydholm A, et al. Clinicopathologic reevaluation of 100 malignant fibrous histiocytomas: prognostic relevance of subclassification. J Clin Oncol. 2001;19:3045-3050.

Reprints: Pelle Gustafson, MD, PhD, Dept. of Orthopedics, University Hospital, SE-221 85 Lund, Sweden;

Immunohistochemical staining in papillary thyroid carcinoma
Surgical pathologists often find it difficult to determine whether a nodular lesion is the follicular variant of papillary thyroid carcinoma. The authors studied the immunohistochemical expression of HBME-1, CK19, and ret in 232 surgically resected thyroid nodules. Their data indicated that reactivity for HBME-1 may be suggestive of a malignancy since the expression of this marker was not found in 75 benign lesions. Diffuse reactivity for CK19 was not found in 74 benign lesions, follicular carcinomas (0/4), or anaplastic carcinomas (0/2). It was found in one follicular adenoma. Diffuse reactivity for this marker may suggest a carcinoma with papillary differentiation. Reactivity for ret was not identified in any benign lesion (0/75), follicular carcinoma (0/4), or anaplastic carcinoma (0/2). Papillary thyroid carcinomas were reactive for ret, CK19, and HBME-1 in 69 percent, 66 percent, and 55 percent of cases, respectively. In only nine cases (9/138—seven of the follicular variant and two of the classic type) of papillary thyroid carcinoma were all three markers negative. The results of this study suggest that these markers may be useful as an adjunct to morphology in problematic cases.

Cheung CC, Ezzat S, Freeman JL, et al. Immunohistochemical diagnosis of papillary thyroid carcinoma. Mod Pathol. 2001;14:338-342.

Reprints: Dr. Sylvia L. Asa, Dept. of Pathology, University Health Network, 610 University Ave., Toronto, Ontario M5G 2M9 Canada;;
fax: 416-946-6579

Gastric mucosal changes in patients with hyperplastic polyps of the stomach
Endoscopic examination of the stomach is widely performed, and biopsies of gastric hyperplastic polyps are common specimens in the surgical pathology laboratory. The authors reported the findings from 160 patients with gastric hyperplastic polyps and characterized the endoscopic and histologic features of the background gastric mucosa as well as the polyps. They found that hyperplastic polyps were most common in the antrum (60 percent) and were multiple in 20 percent of patients. Intestinal metaplasia of the polyp was uncommon (16 percent), and intrapolyp dysplasia (four percent) and carcinoma (0.6 percent) were rare. The surrounding gastric mucosa, however, showed intestinal metaplasia in 37 percent of patients, adenoma or low-grade epithelial dysplasia in two percent, and synchronous or metachronous carcinoma in six percent. Eighty-five percent of patients had inflammatory mucosal changes of the nonpolyp mucosa, with chronic active H. pylori gastritis in 25 percent, chemical gastritis in 21 percent, and atrophic gastritis of autoimmune or environmental types in 12 percent and eight percent, respectively. The authors stated that their findings further emphasize the importance of biopsy for nonpolypoid gastric mucosa during endoscopic examination.

Abraham SC, Singh VK, Yardley JH, et al. Hyperplastic polyps of the stomach: associations with histologic patterns of gastritis and gastric atrophy. Am J Surg Pathol. 2001;25:500-507.

Reprints: Susan C. Abraham, MD, Div. of Gastrointestinal/Liver Pathology, Dept. of Pathology, Ross Bldg., Room 632, Johns Hopkins University School of Medicine, 720 Rutland Ave., Baltimore, MD 21205-2196;

Foamy gland carcinoma of the prostate
Prostatic adenocarcinoma, composed of cells with a foamy cytoplasm and minimal nuclear atypia, may be difficult to diagnose on needle core biopsy specimens. Further, its deceptively benign appearance may result in inaccurate grading. The authors described six cases of prostatic foamy gland carcinoma in which the amount of carcinoma with a foamy appearance ranged from 16 to 86 percent of total tumor volume. The most important feature for recognizing this variant is the absence of basal cells. Other features that may help include the presence of adjacent adenocarcinoma of the usual type and the reactivity of the cytoplasm of the foamy cells with colloidal iron and Alcian blue stains. The latter feature suggests that the foaminess is due to the presence of mucopolysaccharides. Ultrastructurally, the cytoplasm was noted to contain numerous intracytoplasmic vesicles and polyribosomes. Tumors with foamy cells had combined Gleason scores of nine (one case), seven (four cases), and six (one case). Extraprostatic extension was present in five of six cases, three of which had lymph node metastasis. (The foamy feature was identified in the metastatic component in one case.) One patient developed recurrent disease. Prostatic adenocarcinoma with a foamy gland component may be associated with a high stage and aggressive behavior.

Tran TT, Sengupta E, Yang XJ. Prostatic foamy gland carcinoma with aggressive behavior. Am J Surg Path. 2001;25: 618-623.

Reprints: Ximing J. Yang, MD, PhD, Dept. of Pathology, MC 6101, University of Chicago, 5841 S. Maryland Ave., Chicago, IL 60637;