Atypical Intraductal Hyperplasia Research Articles

Risk factors of breast intraductal lesions in patients without pathological nipple discharge.

The majority of breast cancer arises from the ductal epithelium. It is crucial in the diagnosis and treatment of breast cancer by detecting intraductal lesions at an early stage. The typical clinical characteristic of intraductal lesions is pathological nipple discharge (PND), although many patients with intraductal lesions do not exhibit PND. It is a serious challenge for clinicians to detect patients with intraductal lesions without PND at an early stage. The aim of the present study was to investigate the risk factors associated with intraductal lesions in patients without PND. This retrospective database review, conducted between April 2016 and April 2017, included 370 lesions from 255 patients with intraductal lesions (intraductal papilloma, atypical intraductal hyperplasia, intraductal carcinoma in situ) and non-intraductal lesions (fibroadenoma, adenosis, cysts, lobular carcinoma in situ), diagnosed through surgical pathology. The patients were divided into two groups based on pathological diagnosis and clinical parameters were evaluated using univariate and multivariate analyses. Univariate analysis revealed that 9 of 14 factors were statistically significant. Five factors were identified to be associated risk factors in patients without PND through the multivariate logistic regression analysis: Age between 35 and 49 years and age ≥50 years [odds ratio (OR)=4.749, 95% confidence interval (CI)=2.371-9.513, P<0.001; OR=2.587, 95% CI=2.587-14.891, P<0.001; respectively], non-menstrual breast pain (OR=1.922, 95% CI=1.037-3.564, P=0.038), breast duct dilatation as seen using ultrasonography (OR=9.455, 95% CI=3.194-27.987, P<0.001), lesion distance from nipple ≤2 cm (OR=2.747, 95% CI=1.668-4.526, P<0.001) and lesion size ≤1 cm (OR=1.903, 95% CI=1.155-3.136, P=0.012). In conclusion, for patients without PND but with risk factors, such as the patient being >35 years, with non-menstrual breast pain, breast duct ectasia, lesion distance from nipple ≤2 cm and lesion size ≤1 cm as seen using ultrasonography, clinicians should be highly concerned about the possibility of intraductal lesions, in order to prevent misdiagnosis and reduce the misdiagnosis rate.

Co-expression of p16 and p53 characterizes aggressive subtypes of ductal intraepithelial neoplasia.

In the USA alone, approximately 61,000 new diagnoses of ductal intraepithelial neoplasia 1c-3 (DIN) are made each year. Around 10-20% of the patients develop a recurrence, about 50% of which are invasive. Prior studies have shown that invasive breast carcinomas positive for p16 or p53 have a higher frequency of recurrence and a more aggressive course; however, the co-expression of these markers across the entire spectrum of DIN and its potential correlation with grade of the lesions has not been studied previously. Immunohistochemical staining for p16 and p53 was evaluated on 262 DIN lesions from 211 cases diagnosed between 1991 and 2008. The lesions ranged from DIN1b (atypical intraductal hyperplasia) to DIN3 (DCIS, grade 3) and included 45 cases with associated invasive carcinoma. Frequency of staining for both p16 and p53 increased with increasing grade of DIN. Strong co-expression was found exclusively in higher grade DIN lesions (DIN2 and DIN3) particularly those associated with periductal stromal fibrosis and lymphocytic infiltrate. Strong co-expression was seen in 8 of 12 DIN3 lesions (67%) associated with invasive carcinoma. In conclusion, co-expression of p16 and p53 increases with advancing grade of DIN and is maximal in high grade DIN lesions associated with invasive carcinoma, indicating a more aggressive phenotype. A distinctive variant of DIN with periductal fibrosis and lymphocytic infiltrate invariably falls into the high-grade category, based on either morphology or marker expression. Co-expression of p16/p53 may be of help in distinguishing between high-grade and low-grade DIN lesions.

Application value of end-to-side closed in situ pancreaticojejunostomy in pancreaticoduodenectomy

Objective To explore the application value of end-to-side closed in situ pancreaticojejunostomy in pancreaticoduodenectomy. Methods The clinical data of 22 patients with obstructive jaundice who were admitted to the Second Affiliated Hospital of Harbin Medical University from January to March 2014 were retrospectively analyzed. All the patients were explored whether tumors invaded inferior vena cava, superior mesenteric vein and portal vein after gallbladder decompression under general anesthesia by tracheal intubation. The standard or extended pancreaticoduodenectomy was applied according to the intraoperative results. The method of pancreaticojejunostomy was end-to-side closed in situ anastomosis of pancreatic duct and jejunal seromuscular layer. The operation time, intraoperative blood loss, postoperative gastrointestinal function recovery time, amylase concentration of drainage at postoperative day 1, 3, 5, postoperative complication, pathological classification and duration of hospital stay were observed. Patients were followed up by outpatient examination and telephone interview till May 2014. The out-patient follow-up included color Doppler ultrasound examination of effusion near the pancreatic stump, and the telephone interview included whether there were diarrhea of exocrine pancreatic insufficiency. Measurement data with normal distribution were presented as ±s (range), and measurement data with skewed distribution as M(range). Results All the 22 patients underwent successfully the operation, including 17 undergoing standard pancreaticoduodenectomy and 5 undergoing extended pancreaticoduodenectomy, with end-to-side closed in situ anastomosis of pancreatic duct and jejuna seromuscular layer. The operation time of pancreaticoduodenectomy and end-to-side closed in situ pancreaticojejunostomy were (313±37)minutes (range, 228-360 minutes) and(13±4)minutes (7-22 minutes), respectively. The intraoperative blood loss was (400±207)mL (range, 100-800 mL). The mean tumor size was 3.69 cm2 (range, 0.72-1.68 cm2). The recovery time of gastrointestinal function was (5±2)days (range, 4-7 days). The serum amylase at postoperative day 1, 3, 5 in the 21 patients was (145±30)U/L (range, 116-180 U/L), (136±40)U/L (range, 105-176 U/L), (147±38)U/L (range, 110-175 U/L), and the drainage amylase was (220±56)U/L (range, 172-289 U/L), (240±54)U/L (range, 192-300 U/L), (245±52)U/L (range, 190-298 U/L), respectively. The serum amylase at postoperative day 1, 3, 5 in the patient with pancreatic fistula was 156 U/L, 178 U/L and 177 U/L, and the drainage fluid amylase was 500 U/L, 620 U/L and 605 U/L, respectively. There was 1 patient in the 22 patients with pancreatic duct stent and without death. Among the 4 patients with postoperative complications, 1 patient with grade A postoperative pancreatic fistula recovered after continuous external drainage, the other 3 including 1 case of infection, 1 case of pneumonia and 1 of stress ulcer bleeding also recovered after symptomatic and supportive treatment. Postoperative pathological examinations of the 22 patients showed 12 cases of ductal adenocarcinoma, 2 of neuroendocine tumors, 1 of simple cyst, 1 of cystadenocarcinoma, 1 of squamous carcinoma, 1 of adenocarcinoma, 1 of ampullary carcinoma, 1 of tubular adenoma, 1 of leiomyoma and 1 of atypical intraductal hyperplasia. The average length of hospital stay was (11±3)days (range, 2-15 days). There were no effusion near the pancreatic stump showed in color Doppler ultrasound examination and diarrhea of exocrine pancreatic insufficiency. Conclusion End-to-side closed in situ pancreaticojejunostomy is safe and feasible, and can be applied to any pancreatic duct size and texture. Key words: Obstructive jaundice; Pancreaticoduodenectomy; Closed pancreaticojejunostomy; Pancreatic fistula

Magnetic resonance imaging in patients with nipple discharge: should we recommend it?

Comparing the sensitivity of Contrast-Enhanced Magnetic Resonance Imaging (CEMRI), mammography and ultrasonography in patients with nipple discharge (ND). We retrospectively evaluated 38 women with ND who underwent mammography, ultrasound and 1.5 T CEMRI between March 2007 and July 2009. Imaging findings, pathological diagnosis and follow-up data (mean follow-up: 20 months) were compared. Sensitivity and specificity values were reckoned. Statistical differences in sensitivity were assessed. 5/38 malignancies (13.2%; 3 invasive, 2 intraductal; 4 ipsilateral, 1 contralateral to ND), and 14/38 High-Risk Lesion (HRL--36.8%; 11 intraductal papillomas, 1 papilloma with LCIS, 1 sclerosing papilloma and 1 atypical intraductal hyperplasia, all ipsilateral) were found. CEMRI identified 5/5 cancers and 13/14 HRL (Overall Sensitivity-OSS = 94.7%; Overall Specificity-OSP = 78.9%). 3/5 cancers (1 invasive, 1 in-situ; 1 invasive contralateral) and 2/14 HRL were detected by CEMRI only. Mammography found 2/5 cancer and 3/14 HRL (OSS = 26.3%; OSP = 94.7%). Ultrasound identified 1/5 cancer and 11/14 HRL (OSS = 63.2%; OSP = 84.2). 1/14 HRL was detected by ultrasound only. Compared with mammography and ultrasound, CEMRI showed statistically significantly higher OSS values (p < 0.0001, p = 0.042 respectively). In women with ND, CEMRI should be recommended when conventional imaging is negative. Unexplained ND could be considered an indication for CEMRI.

Frequency of Clinically Occult Intraepithelial and Invasive Neoplasia in Reduction Mammoplasty Specimens: A Study of 516 Cases

Reduction mammoplasty is a frequently performed procedure for the treatment of macromastia and for the achievement of symmetry in breast cancer patients following lumpectomy. Slides from 516 consecutive bilateral reduction mammoplasties performed for macromastia over 15 years were reviewed. Among these, 92 (18%) low-risk ductal intraepithelial neoplasia/intraductal hyperplasia, 28 (5%) ductal intraepithelial neoplasia 1 (1 low-grade ductal carcinoma in situ, 11 atypical intraductal hyperplasia, and 16 flat type), 17 (3%) lobular intraepithelial neoplasia, and 1 (0.2%) tubular carcinoma were identified. The patients were categorized into 3 age groups: <40 (n=352), 40 to 50 (n=107), and over 50 years (n=57); the frequency of the lesions increased with age. These data confirm the low frequency of clinically occult malignancies identified in reduction mammoplasty specimens and provide substantial information about the frequency of a variety of intraepithelial proliferations. Preoperative mammography, specimen orientation, and inking of margins with 1 color are advised when reduction mammoplasty is scheduled for women>or=40 years of age.

Significance of Extent of Lobular Neoplasia on Breast Core Biopsy

Objective We reviewed our excisional biopsy findings in cases when core needle biopsy (CB) found lobular neoplasia (LN) as a primary diagnosis. We also correlated the core needle biopsy and excisional biopsy findings according to the quantitative and qualitative extent of lobular neoplasia found on the core needle biopsy specimen. Design We reviewed the mammographic findings and correlated the histopathological findings of core needle biopsy and subsequent surgical excision in cases when the diagnosis on core needle biopsy was lobular neoplasia. On the core needle biopsy the quantity of lobular neoplasia was categorized as involving one to two lobules, three to four lobules, or more than four lobules and qualitatively the lobular neoplasia was characterized as either atypical lobular hyperplasia (ALH) or lobular carcinoma in situ (LCIS). Results In the twelve cases with lobular neoplasia alone on core needle biopsy, excision showed lobular neoplasia in seven cases, atypical ductal hyperplasia (ADH) in three cases, intraductal carcinoma in one case, and in one case infiltrating carcinoma (17% with carcinoma). From the ten cases when the diagnosis was lobular neoplasia and atypical intraductal hyperplasia on core needle biopsy, excision showed lobular neoplasia in four cases, ADH in two cases, intraductal carcinoma in two cases, and in two cases infiltrating carcinoma (40% with carcinoma). The quantitative or qualitative characterization of the lobular neoplasia on core needle biopsy did not prove to be a predictor of outcome in the subsequent excisional biopsies. Conclusions Although these results must be confirmed by larger studies our findings suggest that excisional biopsy should be performed when lobular neoplasia is diagnosed on core needle biopsy regardless of the radiologic findings or extent of lobular neoplasia on core needle biopsy.

Cytological criteria for the diagnosis of intraductal hyperplasia, ductal carcinoma in situ, and invasive carcinoma of the breast.

The advent of mammography screening presents a diagnostic challenge to the cytopathologist as an increasing proportion of breast lesions requiring investigation will be nonpalpable and up to 40% will be accounted for by atypical intraductal hyperplasia and ductal carcinoma in situ, as opposed to previously, when these lesions represented less than 10% of palpable tumors. We studied 133 fine-needle aspirates from breast tumors and found that nuclear morphology, myoepithelial cells, signs of invasion, and degree of cellular dissociation are among the most potent factors discriminating between benign epithelial proliferations, atypical intraductal hyperplasia, ductal carcinoma in situ, and invasive carcinoma.

Endometase/matrilysin-2 in human breast ductal carcinoma in situ and its inhibition by tissue inhibitors of metalloproteinases-2 and -4: a putative role in the initiation of breast cancer invasion.

Local disruption of the integrity of both the myoepithelial cell layer and the basement membrane is an indispensable prerequisite for the initiation of invasion and the conversion of human breast ductal carcinoma in situ (DCIS) to infiltrating ductal carcinoma (IDC). We previously reported that human endometase/matrilysin-2/matrix metalloproteinase (MMP) 26-mediated pro-gelatinase B (MMP-9) activation promoted invasion of human prostate carcinoma cells by dissolving basement membrane proteins (Y. G. Zhao et al., J. Biol. Chem., 278: 15056-15064, 2003). Here we report that tissue inhibitor of metalloproteinases (TIMP)-2 and TIMP-4 are potent inhibitors of MMP-26, with apparent K(i) values of 1.6 and 0.62 nM, respectively. TIMP-2 and TIMP-4 also inhibited the activation of pro-MMP-9 by MMP-26 in vitro. The expression levels of MMP-26, MMP-9, TIMP-2, and TIMP-4 proteins in DCIS were significantly higher than those in IDC, atypical intraductal hyperplasia, and normal breast epithelia adjacent to DCIS and IDC by immunohistochemistry and integrated morphometry analysis. Double immunofluorescence labeling and confocal laser scanning microscopy revealed that MMP-26 was colocalized with MMP-9, TIMP-2, and TIMP-4 in DCIS cells. Higher levels of MMP-26 mRNA were also detected in DCIS cells by in situ hybridization.

Use of keratin 35betaE12 as an adjunct in the diagnosis of mammary intraepithelial neoplasia-ductal type--benign and malignant intraductal proliferations.

A variety of studies have investigated the role of low molecular weight (LMW) and high molecular weight (HMW) cytokeratin (CK) expression in the normal breast and invasive breast carcinomas. A few studies with small numbers of cases have addressed this issue in intraductal proliferations of the breast. This study investigates the expression of these CKs in a large series of ductal intraepithelial neoplasias of the breast. We examined 150 ductal carcinomas in situ (DCIS), 35 cases of intraductal hyperplasia (IDH), and 15 cases of atypical intraductal hyperplasia (AIDH). Immunohistochemistry was performed using monoclonal antibodies against CK-34betaE12 (HMW CK), CK-8, and CK-19 (LMW CK) on formalin-fixed, paraffin-embedded tissue. The intensity (0, +1, +2, +3) and percentage of positive intraductal cells (0-100%) were multiplied to obtain a score from 0 to 300. The immunoprofiles of IDH, AIDH, and DCIS were categorized into four groups showing negative or low (0-60), moderate (61-100), high (101-200), and very high (201-300) scores. All cases of IDH showed an intensely positive reaction (high to very high scores) for CK-34betaE12. In contrast, 90% of the DCIS showed a negative or only focal and weak reaction (negative or low score) for this antigen. The remaining 10% of DCIS showed a positive immunoreaction for CK-34betaE12 with moderate to high scores. All cases of florid IDH and 96% of cases of DCIS expressed CK-8 intensely with high to very high scores. Although CK-19 was strongly expressed in 97% of cases of IDH (high to very high scores), a very high score was also found in 80% of cases of DCIS that were positive for CK-19. Of the 15 AIDHs, 80% had a negative or only focal reaction (negative or low score) for CK-34betaE12 and the remaining 20% had a moderate to high score for this antigen. Although CK-8 was strongly positive in 87% of cases of AIDH (high to very high scores), only 53.5% of AIDHs showed intense positivity for CK-19. The present study clearly shows that the immunoprofile of IDH is different from DCIS as far as HMW CK is concerned. Although florid IDH is characterized by a diffuse and intense immunoreaction for HMW CK, the lack of or only weak positivity for HMW CK (CK-34betaE12) is, in most cases, a hallmark of ductal carcinoma in situ. The immunoprofile of AIDH is very similar to that of DCIS. The expression of CK-8 and CK-19 is not useful in separating the various categories of ductal intraepithelial proliferations of the breast. We recommend the use of CK-34betaE12 as an adjunct in the diagnosis of a variety of problematic intraductal proliferations of the breast.

Expression of S100-α and S100-β in atypical papilloma, atypical papillomatosis and atypical intraductal hyperplasia of the breast

Expression of S100-α and S100-β in atypical papilloma, atypical papillomatosis and atypical intraductal hyperplasia of the breast

Intraductal proliferations of the breast: a review of histologic criteria for atypical intraductal hyperplasia and ductal carcinoma in situ, including apocrine and papillary lesions.

The proliferation of intraductal mammary epithelium forms a continuum that begins with intraductal hyperplasia and ends with ductal carcinoma in situ. Atypical intraductal hyperplasia is the midpoint between the benign and malignant poles of this proliferative continuum. By defining the histological criteria for atypical intraductal hyperplasia, distinction from ordinary intraductal hyperplasia and the noncomedo forms of ductal carcinoma in situ becomes easier. Histopathologic criteria for atypical intraductal hyperplasia, ductal carcinoma in situ, and intraductal hyperplasia and their relative risks for the development of invasive breast carcinoma are reviewed. Related topics of intraductal apocrine and papillary proliferative lesions also are discussed.

Morphofunctional Features of Intraductal Hyperplasia, Atypical Intraductal Hyperplasia, and Various Grades of Intraductal Carcinoma

Abstract: The spectrum of epithelial proliferations within the mammary duct system includes lobular, ductal, and papillary patterns of proliferation. Among those with a ductal growth pattern, the highest proportion qualifies as ordinary intraductal hyperplasia (IDH), a small proportion shows atypical intraductal hyperplasia (AIDH), and a steadily increasing percentage is composed of intraductal carcinomas (IDCA). AIDH and some variants of IDCA share many characteristics and their distinction can be quite troublesome, in some cases relying completely on an arbitrary quantitative criterion. IDH, however, is quite distinctive from both a morphologic and biologic standpoint and should not be confused with AIDH. This review discusses our criteria for diagnosing IDH, AIDH, and IDCA, followed by a review of the common subtypes of IDCA and a presentation of our approach to grading IDCA. The clinical significance and expression of estrogen and progesterone receptor (ER and PR), as well as expression of Ki67 and p53 in IDH, AIDH, and various grades of IDCA are presented.

Gynecomastia with Unusual Intraductal “Clear Cell” Changes Mimicking Pagetoid Ductal Spread of Lobular Neoplasia

This report describes a case of unusual intraductal "clear cell" changes of male breast that mimicked pagetoid ductal spread of lobular neoplasia. The lesion developed inside a nodule of gynecomastia of the left breast in a 56 year-old man. Immunohistochemically, the enlarged clear cells reacted positively with epithelial membrane antigen, low molecular weight cytokeratin and three breast markers (i.e.: gross cystic disease fluid protein-15 and -44 and estrogen receptors). They were negative for high molecular weight cytokeratin, muscle-specific actin, desmin and vimentin. Differential diagnoses included pagetoid ductal involvement by lobular neoplasia (i.e.: lobular carcinoma in situ and/or atypical lobular hyperplasia), pagetoid growth of intraductal carcinoma, atypical intraductal hyperplasia, and unusual intraductal myoepithelial proliferative lesion.

Immunoreactivity with monoclonal antibody A-80 and nuclear DNA content in benign and malignant human breast disease

Immunohistochemical analysis with the monoclonal antibody (MoAb) A-80, recognizing a tumor-associated cytoplasmic mucin-type glycoprotein, and cytometric nuclear DNA assessment were performed on 314 surgical specimens of the human mammary gland. The series included 36 benign conditions, 34 epithelial hyperplasias, 40 carcinomas in situ, and 204 primary invasive carcinomas. Normal breast parenchyma, benign tumors, and other nonmalignant lesions were all of DNA diploid (euploid) type and rarely expressed the A-80 glycoprotein. Differences in MoAb A-80 immunoreactivity and nuclear DNA content were noted among subtypes of epithelial hyperplasias. Fifteen of 34 epithelial hyperplasias were of DNA aneuploid type and the majority were A-80 immunoreactive. Of these 15 immunoreactive aneuploid epithelial hyperplasias, atypical intraductal hyperplasia was the most common subgroup. None of the 19 epithelial hyperplasias of DNA euploid type immunoreacted. Most of the intraductal (33 of 40) and invasive (180 of 204) carcinomas immunostained with MoAb A-80. The majority of the A-80 immunoreactive malignant tumors were of DNA aneuploid type (26 of 33 carcinomas in situ and 108 of 180 invasive mammary carcinomas). The results suggest that expression of the A-80 glycoprotein occurs at an early stage of malignant transformation. Genetically stable (euploid) mammary tumors seem to immunoreact with MoAb A-80 less frequently than genetically unstable (aneuploid) tumor variants. Combined analysis with MoAb A-80 and of nuclear DNA content in premalignant and malignant mammary lesions could be a useful tool of differential diagnostic and prognostic value.

A comparison of the results of long-term follow-up for atypical intraductal hyperplasia and intraductal hyperplasia of the breast

Follow-up information was obtained on 199 women with breast biopsy specimens containing intraductal epithelial proliferation. The proliferations were divided into regular or ordinary intraductal hyperplasia (IDH) (117 cases) and atypical intraductal hyperplasia (AIDH) (82 cases). The average length of follow-up was 14 years for the patients with IDH and 12.4 years for the patients with AIDH. Of the 117 patients with ordinary IDH, carcinoma subsequently developed in six (5%); three of these were invasive carcinomas (2.6%). All three invasive carcinomas were in the ipsilateral breast, but of the three intraductal carcinomas (IDCa), two were in the contralateral breast. Of the 82 patients with AIDH, invasive carcinoma subsequently developed in eight (9.8%); six of these were located in the ipsilateral breast and two in the contralateral breast. One of these six patients died of disseminated carcinoma. The average interval to the subsequent carcinoma (intraductal and invasive carcinoma) was about the same in the two groups (8.3 years for AIDH and 8.8 years for IDH lacking atypia). When considering only subsequent invasive carcinomas, the interval was 8.3 years for the AIDH and 14.3 years for the IDH lacking atypia. Of the 14 patients with IDH and a family history of breast carcinoma, invasive carcinoma subsequently developed in one (7%) as compared with two (2%) of the 91 with a negative family history. Among patients with AIDH, invasive carcinoma subsequently developed in two of the 13 (15%) of those with a family history of breast carcinoma as compared with one of 57 (1.8%) of the women with a negative family history. The presence of atypia in epithelial hyperplasia is a significant factor in increasing the likelihood of the development of subsequent invasive carcinoma (P = 0.03; two-tailed test). Of women with AIDH, invasive carcinoma subsequently developed in 17% of those with sclerosing adenosis (SA) as compared with 4.2% of those without it. Therefore, SA may be a contributing factor to increased risk. A positive family history also appears to increase the likelihood of the subsequent development of invasive carcinoma, particularly in patients with AIDH.

Immunohistochemical Staining with Monoclonal Ab B72.3 in Benign and Malignant Breast Disease

A variety of benign and malignant breast lesions were evaluated for their reactivity with the monoclonal antibody B72.3. The lesions included invasive duct carcinoma (15 cases), apocrine carcinoma (18 cases, nine invasive and nine in situ lesions), well-differentiated (tubular) carcinoma (15 cases), invasive lobular carcinoma (10 cases) and lobular neoplasia (10 cases), intraductal hyperplasia (nine cases), atypical intraductal hyperplasia (eight cases), intraductal carcinoma (15 cases), sclerosing adenosis (15 cases), and apocrine metaplasia (24 cases). Only 20% of the invasive ductal carcinomas and 27% of the intraductal carcinomas showed a positive reaction for B72.3. Ten percent of the lobular neoplasias and 25% of the invasive lobular carcinoma reacted with B72.3. None of the 15 tubular carcinomas or the 15 cases of sclerosing adenosis reacted. One of eight examples of atypical intraductal hyperplasia (12.5%) showed a positive reaction, but none of the nine intraductal hyperplasias reacted with B72.3. The most consistently positive results were observed in cases displaying apocrine metaplasia. A positive reaction was observed in 23 of the 24 cases of apocrine metaplasia (96%) and 17 of 18 cases of apocrine carcinoma (94%). Thus we conclude that B72.3 is neither specific nor sensitive for the detection of malignant breast lesions. However, it does appear to be a valuable marker for the presence of apocrine differentiation, which is not a known precursor of carcinoma.

Latent Prostatic Carcinoma: Pathological and Epidemiological Aspects

In conclusion, a review of the epidemiology and pathology of latent prostatic cancer suggests this tumor to be the probable initial phase of a biological continuum that ends with metastatic cancer. Histological grade and tumor volume are highly correlated, as are histological grade and mitotic index. It has also been suggested that atypical intraductal hyperplasia is, in turn, a precursor of carcinoma. This concept gains support from the close association of the two conditions among younger (less than 60 years of age) patients and from their similar mitotic and labeling indices.

The ABO(H) cell surface antigens in carcinoma and benign lesions of the breast.

The ABO(H) cell surface antigens of 13 breast carcinomas and 17 benign breast lesions were tested with a specific red cell adherence assay (SRCA). All 13 breast carcinomas, including 2 lobular carcinomas in situ and 1 noninfiltrating ductal carcinoma, had lost their ABO(H) surface antigens. Fourteen of 17 benign breast lesions had retained their ABO(H) surface antigens. The benign lesions losing their antigens were 1 case each of atypical intraductal hyperplasia, sclerosing adenosis, and intraductal papilloma. SRCA may be a predictor of which benign breast lesions are in fact premalignant.

Mucin-producing carcinoma of the breast. Tissue culture, histochemical and electron microscopic study.

Mucin-producing carcinoma of the female breast was studied by histochemistry, electron microscopy and tissue culture. The tumor cells and lakes of secretion contained strong and weak acidic mucins. Weakly acidic mucins were abundant in areas of adjacent atypical intraductal hyperplasia. Mucin production in the benign atrophic areas was scanty and mainly of the neutral variety. Electron microscopy revealed elaborate organelle morphology as compared to the simple structure of the more common infiltrating duct carcinoma. In cell culture the tumor cells proliferated and produced mucin for 6 weeks through 2 subcultures.