Proximal small-bowel mucosal villous intraepithelial lymphocytes.

Small-bowel biopsies are routinely obtained from adult patients as a screening tool to evaluate the possibility of gluten sensitivity (GS). Previous morphological criteria of GS including completely flattened villi are usually absent. In the context of screening for GS, an altered distribution density pattern of villous intraepithelial lymphocytes (IELs) is probably the most sensitive morphological feature to suggest the possibility of GS and prompt the initiation of further medical evaluation. Altered villous IEL density distribution is a more sensitive screening feature than villous IEL counts. With increased small-bowel GS screening biopsies, occasional adults without GS with complete villous flattening and numerous villous IELs are encountered. These patients are usually incorrectly diagnosed with GS. However, they do not respond to a gluten-free diet and slowly improve over months.

Clinicopathologic implications of E-cadherin reactivity in patients with lobular carcinoma in situ of the breast.

BACKGROUND: The current study addressed two questions pertaining to lobular carcinoma in situ (LCIS) of the breast. First, does the risk of a subsequent carcinoma decrease over time after an LCIS biopsy and second, what is the clinical significance of E-cadherin-reactive LCIS? METHODS: Eighty-two consecutive patients with a biopsy containing LCIS only, no prior history of breast carcinoma, and follow-up information available for the period 1955-1976 were reviewed. No patients underwent a mastectomy for LCIS. Four hundred eighty-six sections were stained with E-cadherin. E-cadherin reactivity was correlated with clinicopathologic features of the LCIS and subsequent tumors. The mean number of blocks stained per case was 5.9. The mean follow-up period was 21.6 years. RESULTS: Sixteen patients (19.5%) developed 21 subsequent invasive carcinomas (9 ipsilateral, 2 contralateral, and 5 bilateral carcinomas). The 10-year and 20-year actuarial rates of developing subsequent carcinoma were 7.8% and 15.4%, respectively. Six of the 21 carcinomas (29%) developed after 20 years. Nine LCIS cases (10.9%) had focal E-cadherin reactivity. When compared with patients with nonreactive LCIS, patients with E-cadherin-reactive LCIS more frequently developed a subsequent ipsilateral carcinoma that had a ductal component (55.5% vs. 12.3%; P < 0.01). The subsequent carcinomas also developed after significantly shorter time periods (mean of 7.6 years vs. 19.6 years; P < 0.01). CONCLUSIONS: LCIS appears to confer a persistent, increased risk of subsequent breast carcinoma that does not appear to decrease over time. E-cadherin reactivity appears to identify a subset of LCIS patients with risk factors for subsequent carcinoma similar to those of patients with low-grade intraductal carcinoma.

Mucinous and nonmucinous bronchioloalveolar adenocarcinomas have distinct staining patterns with thyroid transcription factor and cytokeratin 20 antibodies.

We studied 14 mucinous and 26 nonmucinous bronchioloalveolar adenocarcinomas (BACs) with thyroid transcription factor (TTF), cytokeratin (CK) 7, CK20, and villin to characterize their staining patterns with these antibodies and identify staining differences between the neoplasms. We also stained 11 mucinous colon adenocarcinomas with the same antibodies to compare their reaction patterns with mucinous BACs. All pulmonary neoplasms were confirmed pulmonary primary BACs. Three (21%) of 14 mucinous neoplasms had weak TTF reactivity in fewer than 25% of neoplastic cell nuclei, and the other 11 (79%) were nonreactive. In contrast, 24 (92%) of 26 nonmucinonus BACs were strongly TTF reactive. Eleven mucinous BACs (79%) had CK20 reactivity in more than 25% of neoplastic cells, whereas only 1 nonmucinous BAC (4%) had reactivity in fewer than 50% of the cells. One mucinous BAC (7%) had villin reactivity in approximately 10% of the neoplastic cells. All mucinous colon adenocarcinomas were diffusely reactive with CK20 and villin. Mucinous and nonmucinous BACs have disparate staining patterns with TTF and CK20. Mucinous BACs are usually TTF nonreactive and CK20 reactive, but nonreactive with villin, which distinguishes them from mucinous colon adenocarcinomas.

Epidermal growth factor receptor immunohistochemical reactivity in patients with American Joint Committee on Cancer Stage IV colon adenocarcinoma: implications for a standardized scoring system.

BACKGROUND: An epidermal growth factor receptor (EGFR) immunohistochemical detection system currently is being developed. The current study attempts to address background EGFR reactivity issues before determining the optimum EGFR scoring system. METHODS: Tissue sections from 102 patients with T3N1-2M1 colon adenocarcinoma were stained with a prototype EGFR detection system. The number of cases, location, percentage, and intensity of reactive cells (0+ [none] to 3+ [strong]) were scored and compared with the length of survival. RESULTS: Approximately 75.5% of the adenocarcinoma cases had EGFR reactivity; 31.4% of the tumors had 3+ reactivity in 10-50% of the neoplastic cells and 3.9% had 3+ reactivity in > 50% of cells. Increased numbers of reactive cells per case predominantly resulted from increased 3+ reactivity. The mean percentage of 2+ (moderate) and 3+ reactive cells per case increased in the regions of deepest invasion. The mean percentage of 3+ reactivity per case was significantly greater in the deepest tumor region compared with the superficial region (16.9% vs. 7.9%; P = 0.004). EGFR reactivity in metastases appeared to have the strongest correlation with reactivity in the deep regions of colon adenocarcinoma. An increasing percentage of 2+ and 3+ or 3+ only reactivity in the deep region was found to have the strongest correlation with decreased survival (P = 0.0252). CONCLUSIONS: EGFR reactivity of 2+ and 3+ may provide a framework for a scoring system. It may be important to evaluate EGFR reactivity in the deepest region of tumor invasion because this region appears to contain the largest percentage of 3+ reactive cells and appears to have the strongest correlation with survival length and EGFR reactivity in lymph node and liver metastases.

Recent pathology related advances in colorectal adenocarcinomas.

This brief review addresses some new developments in the understanding of the molecular pathogenesis of colorectal cancer, including the mismatch repair protein mechanism of colorectal adenocarcinoma carcinogenesis. The second part of this review summarizes recent improvements in the pathological evaluation of colorectal resection specimens, and highlights the advantage seen in the resulting improved quality of gross dissection provided by the use of highly trained non-medical pathology assistants. Topics also covered include optimum methods of assessment of radial resection margins, the accuracy of measured margin distances, the assessment of adenocarcinoma involvement of the peritoneal serosal surface, improved methods of lymph-node recovery from colorectal adenocarcinoma resection specimens and the recently recognized adverse prognostic significance of extranodal pericolonic tumour deposits. Formats for standardized reporting of colorectal resection specimens are presented as a means to improve quality and consistency of pathological data recording and collection.

WT1 is an integral component of an antibody panel to distinguish pancreaticobiliary and some ovarian epithelial neoplasms.

We investigated whether a panel of antibodies including WT1 could separate pancreaticobiliary and ovarian carcinomas by staining 64 pancreaticobiliary adenocarcinomas, 41 ovarian serous carcinomas, and 12 primary ovarian mucinous neoplasms with WT1, cytokeratin (CK) 17, CK20, carcinoembryonic antigen (CEA), and CA-125. Moderate or strong intensity reactivity in more than 25% of cells was a positive result. Of the ovarian serous carcinomas, 38 (93%) were WT1 reactive and 22 (54%) WT1 positive, 9 (22%) had CK20 reactivity, and 3 (7%) were CK20 positive in fewer than 50% of cells. All were CK17 or CEA nonreactive. Of the ovarian mucinous neoplasms, all were WT1 and CK17 nonreactive and 11 (92%) were CEA reactive, 8 (67%) CEA positive, 10 (83%) CK20 reactive, and 6 (50%) CK20 positive. Of the pancreaticobiliary adenocarcinomas, 19 (30%) were CK20 positive, 27 (42%) CK17 positive, and 52 (81%) CEA positive. All were WT1 nonreactive. A panel including WT1, CK17, CK20, and CEA is useful to distinguish pancreaticobiliary and ovarian serous carcinomas. Extensive CK17 reactivity is supportive of a pancreaticobiliary adenocarcinoma when the differential diagnosis includes ovarian mucinous neoplasm. None of the antibodies positively identified ovarian mucinous neoplasms.

Morphologic features suggestive of gluten sensitivity in architecturally normal duodenal biopsy specimens.

We studied small bowel biopsy specimens with architecturally normal villi from 78 adult patients with potential gluten sensitivity (GS) and correlated them with outcome to characterize morphologic features that would allow a pathologist to suggest GS. No patient had a previous GS diagnosis. Twelve study patients had GS. The mean number of intraepithelial lymphocytes (IELs) per 20 enterocytes from the tips of 5 random villi was significantly greater in GS than non-GS biopsy samples, but the groups overlapped significantly, making the number diagnostically useful only when markedly increased. Crypt mitoses counts had similar relationships. Twelve patients had an even distribution of IELs along villus sides and over tips (3/66 [5%] non-GS patients, 9/12 [75%] GS patients). Non-GS patients had a decrescendo pattern of IELs along the sides of villi. Architecturally normal small bowel biopsy specimens with an appreciable, continuous, even distribution of IELs along the sides and tips of villi and a mean of 12 or more IELs in the tips of several villi are suggestive of GS. Pathologists should be watchful for these morphologic features in small bowel biopsy specimens to suggest GS.

Cytokeratins 7, 17, and 20 reactivity in pancreatic and ampulla of vater adenocarcinomas. Percentage of positivity and distribution is affected by the cut-point threshold.

We studied reactivity of cytokeratins (CK) 7, 17, and 20 in 64 pancreaticobiliary adenocarcinomas to examine the effect of different cut-point thresholds on "positive" results, compare ampulla of Vater and pancreas adenocarcinomas, and provide additional experience with CK17 reactivity. Almost all neoplasms had extensive CK7 reactivity. The number of CK20-positive cases decreased from 29 (45%; any stained cells) to 19 (30%; > 25% staining) to 14 (22%; > 50% staining) with an increasing threshold of reactive cells. Similar shifts in the distribution of CK7 and CK20 reactivity occurred when different thresholds of reactivity were used for a positive result. There were no differences in CK7 or CK20 reactivity in pancreas only, ampulla only, and neoplasms involving both sites. Of 64 adenocarcinomas, 29 (45%) had no or single-cell CK17 reactivity, and 19 (30%) had reactivity in more than 50% of neoplastic cells. Ampulla of Vater and pancreas adenocarcinomas have similar CK immunophenotypes that cannot assist in distinguishing ampullary from pancreatic neoplasms on endoscopically procured tissue. CK17 staining occurs in approximately 50% of pancreaticobiliary adenocarcinomas and is usually patchy. Single antibody staining results, especially CK7 and CK20 coordinate reactivity, are influenced by the reactivity threshold used.

Trovafloxacin hepatotoxicity.

A 19-year-old woman was treated for recurrent sinusitis with oral trovafloxacin and developed acute hepatitis and peripheral eosinophilia, with hepatosplenomegaly and ascites. Laparoscopic liver biopsy showed extensive centrilobular hepatocyte necrosis, likely causing venooclusive disease-like signs and symptoms. Clinical and laboratory abnormalities resolved completely after prolonged treatment with steroids. The temporal relationship between trovafloxacin and the onset of hepatitis favors this drug as a culprit.

E-cadherin reactivity of 95 noninvasive ductal and lobular lesions of the breast. Implications for the interpretation of problematic lesions.

Studies suggest that E-cadherin is useful to classify epithelial breast lesions as ductal or lobular, but extensive experience with this antibody is lacking. We studied reactivity of lesions with classic and indeterminate morphologic features. We reviewed 95 lesions and divided them into unanimous and nonunanimous diagnosis groups; the unanimous group served as benchmark lesions to which E-cadherin reactivity could be standardized and compared. All 37 ductal lesions in the unanimous group had strong, diffuse E-cadherin reactivity. Two of 22 classic lobular carcinoma in situ (LCIS) lesions had sparse E-cadherin-reactive lobular cells within a few terminal duct lobular units. Neither displayed transition from nonreactive to reactive cells. Of 36 lesions in the nonunanimous group, 19 had insufficient morphologic features for definitive classification. Only 6 of 19 were E-cadherin reactive, including several minimally proliferative lesions. The other 17 lesions in the nonunanimous group had LCIS and ductal carcinoma in situ (DCIS) features. All had no E-cadherin, or strong membrane reactivity of constituent cells in varying proportions, without a transition between reactive and nonreactive cells. Results suggest that the majority of morphologically nondiagnostic atypical lesions are lobular, including those associated with DCIS. E-cadherin seems to be absent in most lobular lesions.

Accelerated treatment of breast cancer.

PURPOSE: Radiation therapy (RT) restricted to the tumor bed, by means of an interstitial implant, and lasting 4 to 5 days after lumpectomy was prospectively evaluated in early-stage breast cancer patients treated with breast-conserving therapy (BCT). The goals of the study were to determine whether treatment time can be reduced and whether elective treatment of the entire breast is necessary. MATERIALS AND METHODS: Between January 1993 and January 2000, 174 cases of early-stage breast cancer were managed with lumpectomy followed by RT restricted to the tumor bed using an interstitial implant. Each brachytherapy patient was matched with one external-beam RT (ERT) patient derived from a reference group of 1,388 patients treated with standard BCT. Patients were matched for age, tumor size, histology, margins of excision, absence of an extensive intraductal component, nodal status, estrogen receptor status, and tamoxifen use. Median follow-up for both the ERT and brachytherapy groups was 36 months. RESULTS: No statistically significant differences were noted in the 5-year actuarial rates of ipsilateral breast treatment failure or locoregional failure between ERT and brachytherapy patients (1% v 0%, P =.31 and 2% v 1%, P =.63, respectively). In addition, there were no statistically significant differences noted in rates of distant metastasis (6% v 3%, P =.24), disease-free survival (87% v 91%, P =.55), overall survival (90% v 93%, P =.66), or cause-specific survival (97% v 99%, P =.28). CONCLUSION: Accelerated treatment of breast cancer using an interstitial implant to deliver radiation to the tumor bed alone over 4 to 5 days seems to produce 5-year results equivalent to those achieved with conventional ERT. Extended follow-up will be required to determine the long-term efficacy of this treatment approach.

Relationship between excision volume, margin status, and tumor size with the development of local recurrence in patients with ductal carcinoma-in-situ treated with breast-conserving therapy.

BACKGROUND AND OBJECTIVES: We reviewed our institution's experience treating patients with ductal carcinoma-in-situ (DCIS) with breast-conserving therapy (BCT) to help define the interrelationship between excision volume, margin status, and tumor size with local recurrence. METHODS: From January 1980 to December 1993, 146 patients received BCT for DCIS. All patients underwent excisional biopsy and 95 cases (64%) underwent re-excision. Each patient received whole breast radiation to a median dose of 45 Gy. An additional 139 cases (94%) received a supplemental boost to the tumor bed (median total dose 60.4 Gy). The median follow-up is 7.2 years. RESULTS: Seventeen patients developed an ipsilateral breast failure for a 5- and 10-year actuarial rate of 10.2 and 12.4%, respectively. On multivariate analysis, patient age, margin status, the number of slides containing DCIS, the number of DCIS/cancerization of lobules (COL) foci near (< 5 mm) the margin, and a smaller volume of excision (< 60 cm(3)) were all independently associated with outcome. Although the local recurrence rate generally decreased as margin distance increased, these differences did not achieve statistical significance unless the volume of excision was taken into consideration. CONCLUSIONS: These findings suggest that the success of BCT is directly related to the degree of surgical removal of DCIS and that margin status alone may be suboptimal in defining excision adequacy.

The effect of electrothermal cautery-assisted resection of diminutive colonic polyps on histopathologic diagnosis.

We examined diminutive colonic polyps to identify relationships between thermal electrocoagulation or resection trauma cytologic artifacts, type of thermal electrocoagulation, polyp size, and the interobserver variation among 3 pathologists. The 3 pathologists independently evaluated 119 colonic polyps 5 mm or less in maximum dimension for diagnosis and degree of thermal electrocoagulation or resection trauma cytologic artifacts. The maximum dimension of the polyps and type of thermal electrocoagulation were recorded. The average percentage of polyps in which a definitive diagnosis could not be made because of cytologic artifacts was 16.5% (range, 11.8%-19.3%). Decreasing polyp size was associated linearly with the inability to make a definitive diagnosis owing to cytologic artifacts. Polyps smaller than 2 mm significantly more often could not be definitively diagnosed by at least 1 pathologist owing to cytologic artifacts, including some polyps that were excised without thermal electrocautery. Interobserver variation increased with decreasing polyp dimension. Two millimeters seems to represent a cut point, below which the likelihood that a definitive diagnosis can be made can be increased if thermal electrocoagulation is used. This small size seems to make them especially susceptible to cytologically injurious forces.

Portal tract eosinophils and hepatocyte cytokeratin 7 immunoreactivity helps distinguish early-stage, mildly active primary biliary cirrhosis and autoimmune hepatitis.

We studied nondiagnostic liver biopsy specimens from 20 patients with definite primary biliary cirrhosis (PBC) and 18 with definite autoimmune hepatitis (AIH) to identify distinguishing features. All patients had early-stage disease; biopsy specimens were devoid of granulomas or diagnostic features of PBC or AIH. Diagnoses were based on serologic and clinical variables. Sixteen specimens from each group were immunostained with cytokeratin 7. The density of portal tract eosinophils and number with cytokeratin 7-reactive periportal hepatocytes were quantified. Sixteen of 18 patients with AIH and 13 of 20 with PBC had no or minimal bile duct injury. Histologic activity index scores were 5.8 in AIH and 5.7 in PBC. The mean portal eosinophil score was greater in PBC than in AIH. Cytokeratin 7 identified many central bile ducts that were obscured by portal inflammation. The mean periportal cytokeratin 7-reactive hepatocyte score was greater in PBC than in AIH. Portal eosinophils and cytokeratin 7 reactivity in periportal hepatocytes are supportive of PBC rather than AIH. No morphologic features were supportive of AIH. Cytokeratin 7 reactivity in periportal hepatocytes may be an early response to PBC-induced biliary obstruction in other regions of the liver.

Minocycline as a cause of drug-induced autoimmune hepatitis. Report of four cases and comparison with autoimmune hepatitis.

We describe the clinical and liver biopsy morphologic features for 4 patients with minocycline-induced autoimmune hepatitis (group 1). We compared the serum laboratory values and liver biopsy findings from group 1 with those from 10 patients with sporadic autoimmune hepatitis (group 2). All patients in group 1 had positive serum antinuclear antibody titers, but none had positive serum anti-smooth muscle antibody titers. The morphologic findings of group 1 biopsies were those of autoimmune hepatitis in all 4 patients. In addition, 1 of these biopsy specimens also had scattered single eosinophils, unlike autoimmune hepatitis. The mean histologic activity index scores for patients in groups 1 and 2, respectively, were 6.7 and 5.4. No patients in group 1 had marked bridging fibrosis or cirrhosis, compared with 4 of 10 patients in group 2. Minocycline-induced autoimmune hepatitis is usually identical to sporadic autoimmune hepatitis. The absence of eosinophils does not exclude the possibility of a minocycline cause. In the absence of clinical or morphologic differences, a recent ingestion of minocycline should be excluded before the diagnosis of sporadic autoimmune hepatitis is established. Whether the drug is unmasking latent autoimmune hepatitis is unclear.

Gastric cardia intestinal metaplasia: biopsy follow-up of 85 patients.

BACKGROUND: Gastric cardia intestinal metaplasia (CIM), denoted by goblet cells is common. The frequency of persistent CIM is unknown. METHODS: 85 patients with CIM and follow-up endoscopies were prospectively identified during the time period of 10/6/94-12/21/97. The presence of goblet cells was the defining feature of CIM, other metaplastic cell types were not evaluated. AU 85 patients initially had biopsies that straddled the squamocolumnar junction (SCJ) showed CIM, an otherwise normal proximal stomach, lower esophagus, and squamocolumnar junction. The SCJ lay within the 2 cm of mucosa immediately proximal to the uppermost gastric fold and overlaid the junction of the tubular esophagus and the saccular dilatation of the stomach in all patients. The patients underwent endoscopy for many reasons. They were randomly identified based on the absence of a hiatal hernia and the presence of CIM. RESULTS: Ten of the 85 patients had CIM on repeat biopsy. Among patients with no CIM in the first repeat endoscopy, the degree of cardia inflammation decreased between the initial and first repeat endoscopy, whereas there was no change in the amount of inflammation among patients who had CIM in the first repeat endoscopy. The changes in mean inflammation score was significantly different between the two groups (P = .024). Twenty-two patients underwent a second repeat endoscopy and five had a third repeat endoscopy. Including all follow-up biopsies, six of the 85 patients (7%) had CIM. Four patients who did not have CIM on initial repeat endoscopy had CIM on their second repeat endoscopy, probably reflecting sampling issues. None of the biopsies had dysplasia. CONCLUSIONS: Cardia inflammation is a stimulus for cardia intestinal metaplasia, and a reduction in inflammation may allow the metaplastic mucosa to revert to normal.

Ovarian micropapillary serous borderline tumors. Clinicopathologic features and outcome of seven surgically staged patients.

We report the clinicopathologic findings for 7 patients with completely staged ovarian micropapillary serous borderline tumors (MSBTs) to further clarify tumor behavior. None of the MSBTs had microinvasion in the ovarian neoplasm. The MSBT pattern constituted 25% to almost all of the neoplasm. Four were bilateral, and 6 involved the ovarian surface. Five patients had peritoneal implants; 2 were invasive, and 3 were noninvasive MSBTs. Distribution of stages among patients was as follows: IA, 1; IC, 1; IIC, 2; IIIB, 2; and IIIC, 1. Median follow-up was 8.5 years. Four patients were alive and well at the last follow-up visit, including 1 patient with stage IIIC (lymph node metastases) disease who had noninvasive implants (12 years after surgery). One patient who was free of disease died of complications of chemotherapy and abdominal surgery. Two patients died of intra-abdominal neoplastic growth (stages IIC and IIIB) 5 and 9 years after surgery, respectively; both had invasive implants. Without invasive peritoneal implants, MSBTs seem to behave as similar staged nonmicropapillary serous borderline tumors without invasive peritoneal implants. With invasive peritoneal implants, they seem to behave as low-grade carcinomas. Pathologists should recognize MSBT as a neoplasm that can have adverse prognostic features, including invasive peritoneal implants.

Colon signet ring cell adenocarcinoma: immunohistochemical characterization and comparison with gastric and typical colon adenocarcinomas.

Colon signet ring cell adenocarcinomas are uncommon, high-grade neoplasms. Given their rarity, the question of primary colon or metastatic gastric adenocarcinoma frequently arises when signet ring cell carcinoma is seen in a colonoscopic biopsy or in biopsies procured from other regions of the body. A second related question regarding colon and gastric signet ring cell carcinomas is their immunophenotypic similarities with the glandular form of adenocarcinoma in each site. We studied the immunohistochemical phenotype of 14 colonic signet ring cell adenocarcinomas and compared them with immunophenotype of 27 gastric signet ring cell adenocarcinomas. We also compared the immunophenotype of the 27 gastric signet ring cell with the immunophenotype of 19 gastric gland-forming adenocarcinomas, and the immunophenotype of the 14 colonic signet ring cell adenocarcinomas to the immunophenotype of 20 colonic gland-forming adenocarcinomas to identify staining differences in the neoplastic cells of the two architectures. Antibodies studied were cytokeratins 7, 17, 19, and 20, CA 19-9, CA-125. estrogen receptor, and gross cystic disease fluid protein 15. Sixty-four percent of colon signet ring cell adenocarcinomas had either no staining or focal staining with cytokeratin 7 compared with diffuse staining in 63% of gastric signet ring cell adenocarcinomas (P = 0.016). Seventy-two percent of colon signet ring cell adenocarcinomas had diffuse staining with cytokeratin 20 compared with no or focal staining in 50% of gastric signet ring cell adenocarcinomas (P = 0.019). Fifty-seven percent of the colon signet ring cell adenocarcinomas had a cytokeratin 7 (-)/cytokeratin 20 (+) staining pattern compared with 11% of gastric signet ring cell adenocarcinomas (P = 0.004). Forty-four percent of gastric signet ring cell adenocarcinomas had a cytokeratin 7 (+)/cytokeratin 20 (-) pattern, compared with none of the colon signet ring cell adenocarcinomas (P = 0.004). The staining distribution of the antibody battery was similar in colon signet ring cell and colon glandular adenocarcinoma and gastric signet ring cell and gastric glandular adenocarcinomas. When signet ring cell adenocarcinoma is encountered in a colon biopsy, a colon primary is supported if the neoplastic cells have a cytokeratin 7 (-)/cytokeratin 20 (+) staining pattern, and a gastric primary is supported if they have a cytokeratin 7 (+)/cytokeratin 20 (-) staining pattern. The signet ring morphology at each site had an identical immunophenotype as the cells forming their glandular counterpart.

Intraductal carcinoma of the breast: pathologic features associated with local recurrence in patients treated with breast-conserving therapy.

Local excision and radiation therapy is a standard treatment option for duct carcinoma in situ (DCIS) of the breast. There is no consensus regarding the significant histologic features associated with recurrence. The authors studied a large group of patients with mammographically detected DCIS treated with breast-conserving therapy to explore DCIS volume relationships, DCIS features, specimen characteristics, and the effect of patient age at diagnosis. Thirteen patients (10%) developed a recurrent carcinoma in the ipsilateral breast, resulting in 5- and 10-year actuarial recurrence rates of 8.9% and 10.3%, respectively. Local recurrences were identified as a true recurrence/marginal miss (TR/MM) in nine patients, and elsewhere in the breast in four patients. The notable features associated with TR/MM recurrences on univariate analysis included patient age less than 45 years old, six or more slides with DCIS, no microscopic calcifications within DCIS ducts, and five or more DCIS ducts or terminal duct lobular units (TDLUs) with cancerization of lobules (COL) within 0.42 cm of the final surgical margin. DCIS tumor size, nuclear grade, amount of central necrosis, and margin status were not associated with outcome. Multivariate analysis found that the absence of microcalcifications within DCIS ducts, patient age, number of slides with DCIS or TDLUs with COL, and the number of DCIS ducts or TDLUs with COL within 0.42 cm of the final margin were related significantly to TR/MM recurrence. Patients with a total of six or more slides with DCIS, or who have 11 or more DCIS ducts or TDLUs with COL near the final margin are at increased risk of having a substantial volume of residual DCIS in the adjacent unexcised breast. These results suggest that the volume of DCIS in the specimen, and the volume of DCIS near the margin are associated with local recurrence. These features can be used to identify those patients with a higher chance of local recurrence.