Detection of early invasion on the basis of basement membrane destruction in small adenocarcinomas of the lung and its clinical implications.

To evaluate the correlation between the degree of basement membrane (BM) preservation and clinicopathological characteristics in the replacement-growth type (lepidic growth type) of small peripheral adenocarcinomas of the lung, the BM components of 72 surgically resected replacement-growth type adenocarcinomas of the lung, 2 cm or less in diameter, were evaluated immunohistochemically by using a monoclonal antibody to Type IV collagen and polyclonal antibodies to 7S collagen and laminin. The tumors were classified into the following three distinctive histological types according to the condition of the elastic framework: Type I, bronchioloalveolar carcinoma without fibrotic foci; Type II, sclerosing bronchioloalveolar carcinoma without elastic framework destruction; and Type III, sclerosing bronchioloalveolar carcinoma with elastic framework destruction. The BM was well preserved in the area of bronchioloalveolar spread along fully expanded alveoli in all tumor types; however, BM preservation was significantly lost in the areas of collapsed alveoli in Type III tumors. There were no BM component staining reactions in the scarred regions of Type III tumors. In addition, lymph node metastasis was significantly greater in Type III tumors and BM-destroyed tumors. We concluded that the BM was largely destroyed by tumor cell invasion in the scarred region of Type III adenocarcinomas. Type III tumors had discontinuous BMs in the area of collapsed alveoli, indicating that this BM-destructive pattern must be the first step in tumor invasion. Type I and II tumors were concluded to be noninvasive adenocarcinomas, because their BM components were well preserved and they had a good outcome.     

P53 immunohistochemical expression: messages in cervical carcinogenesis

AIMS: The pattern of p53 expression was studied in pre-invasive and invasive cervical carcinoma in an attempt to clarify its role in cervical carcinogenesis. METHODS: A total of 234 invasive cervical carcinomas (152 squamous cell carcinomas, 61 adenocarcinomas and 21 adenosquamous carcinomas) and 16 cervical intraepithelial neoplasia (CIN) I, six CIN II and 25 CIN III were immunohistochemically studied for p53. RESULTS: p53 was detected more frequently in CIN and invasive carcinoma (100% of CIN I, 74.2% CIN II + III and 70.1% invasive carcinoma) compared with benign cervices (P< 0.001); however, only three squamous cell carcinomas, 11 adenocarcinomas and two adenosquamous carcinomas exhibited p53 expression in >75% of tumour nuclei. Six of the 11 adenocarcinomas and both adenosquamous carcinomas were poorly differentiated compared with one of the three squamous carcinomas. p53 immunoreactive cells were randomly distributed in invasive carcinoma, confined to the lower third of the epithelium in CIN I, reached the middle third in 20% of CIN II and upper third in 16.6% of CIN III. CONCLUSIONS: Assuming that p53 immunoreactivity indicates gene mutation when the majority (> 75%) of neoplastic cells express p53, p53 mutations would seem uncommon in cervical carcinogenesis. Nonetheless, glandular malignancies, in particular poorly differentiated variants, may show a higher frequency of mutation. p53 was detected more frequently in CIN I compared with CIN II/III and invasive carcinoma which may be due to p53 protein degradation following interaction with high risk human papillomavirus E6 protein in CIN II/III and invasive carcinoma.     

Micropapillary pattern: a distinct pathological marker to subclassify tumours with a significantly poor prognosis within small peripheral lung adenocarcinoma (</=20 mm) with mixed bronchioloalveolar and invasive subtypes (Noguchi's type C tumours)

AIMS: A micropapillary pattern (MPP) in lung adenocarcinoma, characterized by papillary structures with epithelial tufts lacking a central fibrovascular core, has been reported to be a new pathological marker of poor prognosis. However, its clinicopathological and prognostic significance in small lung adenocarcinomas (相似文献   

Histological progression of small intrapulmonary metastatic tumor from primary lung adenocarcinoma

The histopathology of small metastases is thought to reflect the early metastatic process. To clarify the morphological features of early metastatic tumor progression, we analyzed the histological heterogeneity of many small intrapulmonary metastases. Histological typing based on the World Health Organization classification (bronchioloalveolar carcinoma, acinar, papillary, and solid subtype) was used to evaluate 234 metastases from the primary lung adenocarcinomas of 139 patients. The predominant subtype of metastasis 3 mm or less in diameter was bronchioloalveolar carcinoma when the primary lesion was diagnosed as predominant bronchioloalveolar carcinoma, acinar, and papillary subtype. When the histology of the primary tumor was predominantly a solid subtype, the predominant subtype of metastatic tumor was also a solid subtype. However, analysis of metastases that were more than 3 mm showed that the predominant subtype of the metastasis reflected the predominant subtype of the primary tumor. Furthermore, we evaluated the number of subtypes in primary and metastatic tumors. As the metastasis grew larger, the number of subtypes in the metastatic lesion increased and came close to the number composed in the primary lesion. These findings suggest that implanted cancer cells display lepidic growth in the early metastatic phase and recapitulate the morphological heterogeneity of the original tumor as the metastasis enlarges.     

Loss of alveolar basement membrane type IV collagen alpha3, alpha4, and alpha5 chains in bronchioloalveolar carcinoma of the lung

Type IV collagen, the major component of basement membrane (BM), is composed of six genetically distinct alpha(IV) chains. This study investigated for the first time the expression of these six alpha(IV) chains immunohistochemically, using alpha(IV) chain-specific monoclonal antibodies, in normal lung and in small (less than 2 cm in diameter) adenocarcinoma of the lung with a bronchioloalveolar growth pattern at the periphery. Small adenocarcinomas were histopathologically classified into three subtypes: bronchioloalveolar carcinoma (BAC) without collapse, BAC with collapse, and adenocarcinoma with bronchioloalveolar features. In normal lung, alveolar BM was composed of alpha1(IV)/alpha2(IV) chains and alpha3(IV)/alpha4(IV)/alpha5(IV) chains. In non-collapsed areas of BAC, alveolar BM was composed of linear alpha1(IV)/alpha2(IV) chains and discontinuous alpha3(IV)/alpha4(IV)/alpha5(IV) chains. In collapsed areas of BAC, alveolar BM was composed of linear and thick alpha1(IV)/alpha2(IV) chains only, because of the complete loss of alpha3(IV)/alpha4(IV)/alpha5(IV) chains. In invasive areas of adenocarcinoma with bronchioloalveolar features, alpha1(IV)/alpha2(IV) chains around the cancer cell nests were disrupted, in addition to the complete loss of alpha3(IV)/alpha4(IV)/alpha5(IV) chains. In conclusion, during the process of stromal invasion of lung adenocarcinoma, type IV collagen of alveolar BM is remodelled from the complete type, composed of alpha1(IV)/alpha2(IV)/alpha3(IV)/alpha4(IV)/alpha5(IV) chains, to the incomplete type, composed of only alpha1(IV)/alpha2(IV) chains, before the disruption of alpha1(IV)/alpha2(IV) chains. These findings may help to clarify the molecular mechanisms of cancer invasion.     

MCM2 and Ki-67 expression in human lung adenocarcinoma: prognostic implications.

OBJECTIVE: The expressions of minichromosome maintenance protein 2 (MCM2), Ki-67, and p53 were examined to analyze their pathobiological significance in human lung adenocarcinomas. METHODS: We performed Western blot analysis in six human lung adenocarcinoma cell lines and immunohistochemistry in 145 surgically removed adenocarcinomas to examine the MCM2 expression. Labeling indices (LIs; %) of MCM2, Ki-67, and p53 in the tumor cells were compared with clinicopathological profiles and overall survival rates. RESULTS: MCM2 protein was detected in all cell lines examined, with specific bands. MCM2 LIs were significantly correlated with sex, histological type, differentiation, pathological stage, and LIs of Ki-67 and p53 (p < 0.05). Significantly higher LIs of MCM2 and Ki-67 were noted in the 122 non-pure bronchioloalveolar carcinomas than in the 23 pure bronchioloalveolar carcinomas (p < 0.01), and the prognosis was poorer in the former than in the latter (p < 0.01). Sex, pathological stage, and high LIs of MCM2 and/or Ki-67 were independent prognostic factors (p < 0.05). CONCLUSION: High LIs of MCM2 and/or Ki-67 suggest a poor prognosis in patients with lung adenocarcinoma (non-pure bronchioloalveolar carcinoma).     

TROP-2 and 5hmC expression in follicular-patterned thyroid neoplasm emphasizing tiny well-formed papillae

BackgroundFollicular-patterned thyroid neoplasms (FPTNs), characterized by predominantly follicular growth pattern, represent diverse pathological entities. We aimed to study the nuclear features and the immunoexpression of trophoblast cell-surface antigen 2 (TROP-2) and 5-hydroxymethylcytosine (5hmC) in FPTNs.DesignFPTNs were divided into 4 groups: I) noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP), II) encapsulated follicular variant of papillary thyroid carcinoma (FVPTC) with capsular invasion, III) infiltrative FVPTC, and IV) PTC with a predominantly follicular pattern and well-formed papillae (<1%). Nuclear characteristics were evaluated by image analysis. TROP-2 and 5hmC immunostains were analyzed correlating with histological features using QuPath.ResultsFrom the group I to II, III, and IV, there is a gradual increase in nuclear atypia in terms of the nuclear area, max caliper, perimeter, circularity, and hematoxylin OD means (corresponding to nuclear enlargement, membrane irregularity, and clearing). A similar trend is observed in the TROP-2 expression. 5hmC expression is highly preserved in groups I, II, and III in contrast to a significant loss in group IV. Group IV tumors show more frequent regional lymph node involvement and the highest BRAF V600E mutation rate.ConclusionAmong FPTNs, group IV tumors exhibit the most advanced nuclear atypia, highest TROP-2 expression, significant 5HMC expression loss, frequent regional lymph node involvement, and the highest BRAF V600E mutation rate. Our data further support that the presence of any true papillae should be an exclusion criterion for NIFTP. Therefore, well-formed papillae even if very minute (<1% of the tumor) should not be overlooked.     

Clinicopathologic relevance of apoptotic and proliferative factors in human lung adenocarcinoma: Fas expression correlates with the histologic subtype,but not with the degree of apoptosis

We immunohistochemically examined 141 surgically resected peripheral lung adenocarcinomas for the expression of Fas, single stranded (ss-) DNA and Ki-67, and statistically evaluated the relationship of these parameters with other clinicopathologic variables, including clinical stage, nodal involvement, and histopathologic subtypes classified according to WHO criteria. Fas expression by cancer cells was characteristically localized in the cytoplasm, and the extent of expression correlated well with the degree of Ki-67 reactivity (p = 0.0004), but not with the degree of apoptic occurrence, as assessed by ss-DNA reactivity. Cancer cells of the bronchioloalveolar carcinoma (BAC) subtype without invasive growth exhibited a significantly lower Fas expression than those of other subtypes (p < 0.0001). Positive expression of Fas was frequently associated with a high incidence of nodal involvement and advanced clinical stage, as compared with cases of negative expression (p = 0.0111 and p = 0.0439, respectively). Multivariate analysis revealed that Fas expression significantly correlated with the histologic subtype, but not with tumor size, nodal involvement, or clinical stage. Survival analysis determined by the log-rank test revealed that clinical stage and Ki-67 reactivity were poor prognostic variables, and Fas expression was not statistically significant. Based on these data, intracytoplasmic expression of Fas in cancer cells may participate in the development of resistance to fas-mediated apoptosis.     

Mixed mucinous-type and non-mucinous-type adenocarcinoma of the lung: immunohistochemical examination and K- ras gene mutation

Mucinous-type adenocarcinoma and non-mucinous-type adenocarcinoma are known to be the representative histological subtypes of bronchioloalveolar carcinoma. Mucinous-type adenocarcinoma is also known to carry abnormalities of the K- ras gene at high frequency. However, the mixed subtype of the both mucinous-type and non-mucinous-type adenocarcinoma (mixed-type) has not been analyzed in detail, although its existence has been reported in a few papers. In this study we carried out immunohistochemical and molecular biological analyses of 15 examples of the mixed-type, in comparison with 11 cases of mucinous-type and 21 cases of non-mucinous-type adenocarcinoma. Immunohistochemically, lysozyme - one of the specific markers of mucinous-type adenocarcinoma - was not stained in the mucinous component of the mixed-type. K- ras gene mutations were detected only in mucinous-type (73%) and non-mucinous-type (10%) adenocarcinomas and not in either the mucinous or non-mucinous component of the mixed-type (0%). Therefore, although mixed-type adenocarcinomas consist of tumor cells showing both mucinous and non-mucinous morphology, the mucinous component of this type differs from mucinous-type adenocarcinoma in terms of immunohistochemical features and K- ras gene alteration.     

Ultrastructural comparison of "alveolar" and "solid" areas in bronchioloalveolar carcinoma

The purpose of this study was to compare the ultrastructural features of bronchioloalveolar carcinomas, contrasting the well-differentiated alveolar component and the poorly-differentiated solid component in the same tumor. We studied 7 cases of non-mucinous bronchioloalveolar carcinomas by electron microscopy. Two of these cases showed lamellar bodies in both the alveolar and solid components and the remaining 5 cases revealed Clara cell granules in both components. We conclude that the neoplastic cells in bronchioloalveolar carcinoma retain their ultrastructural phenotypes after becoming invasive carcinoma with loss of alveolar differentiation.     

Relationship between the Extent of Intraductal Component and That of the Invasive Component in Ductal Carcinomas of the Breast

To clarify the relationship between the extent of the intraductal component and the invasive component in cases of invasive ductal carcinoma (IDC) of the breast, we divided 87 such cases into two groups, Group I in which the intraductal component extended for less than 10 mm (36 cases) and Group II in which the intraductal component extended for 10 mm or more (51 cases). On histological slides, there was an association between the extent of the intraductal component and the pattern of invasion. The majority (80.6%) of Group I IDC cases showed an invasive component composed of one invasive nodule, whereas 62.7% of Group II IDC cases showed an invasive component composed of two or more such nodules. On gross and microscopical examination, Group II IDC showed a significantly larger mean tumor size than Group I IDC (23.4 ± 8.9 mm vs. 18.3 ± 6.6 mm, P < 0.002 & 24.1 ± 14.1 mm vs. 17.1 ± 6.5 mm, P<0.002). A similar result was obtained by clinical examination (41.8+17.0 mm vs. 29.5 ± 11.6 mm, P 0.0001). These results suggest that Group II ductal carcinomas may frequently develop multiple stromal invasion, resulting suddenly in a sizeable breast mass perceived by the patient. Acta Pathol Jpn 39: 786-794, 1989.     

Expression of double-stranded RNA-activated protein kinase in small-size peripheral adenocarcinoma of the lung

The authors investigated the protein expression of double-stranded RNA-activated protein kinase (PKR), which was identified by using a previous cDNA microarray study, to discover PKR's correlations with several pathological parameters and to elucidate its role in neoplastic transformation and progression of lung adenocarcinomas. Immunohistochemistry for PKR was performed and a semiquantitative scoring method was calculated based on staining intensity and percentage of immunoreactive tumor cells (high vs low) for one bronchioloalveolar carcinoma (BAC), 16 adenocarcinomas consisting of BAC and invasive carcinoma (mixed) and 21 invasive adenocarcinomas without BAC (invasive). The BAC had high-grade expression and the mixed type tended to more frequently show high-grade expression than the invasive type (P = 0.028). There were no significant associations with age, tumor size, lymph node metastasis, lymphovascular invasion or the pathological stage. The Kaplan-Meier survival curves demonstrated that the patients with high-grade PKR expression had significantly shorter survival periods than those patients with low-grade PKR expression (P = 0.018). These results do not support the concept of PKR as a tumor suppressor in small-size peripheral adenocarcinomas of the lung.     

Coexpression of epithelial membrane antigen (EMA), Ki-1, and interleukin-2 receptor by anaplastic large cell lymphomas. Diagnostic value in so-called malignant histiocytosis

A group of 63 cases of anaplastic large cell lymphomas (variants of diffuse large cell lymphomas often diagnosed as "malignant histiocytosis") was characterized on both morphologic criteria and expression of epithelial membrane antigen (EMA) and Ki-1 antigen (CD30). On the basis of the reactivity of these tumors with anti-EMA and anti-Ki-1 antibodies, four subtypes could be distinguished. In the majority of cases (n = 49), neoplastic cells coexpressed EMA and Ki-1 antigens. Nineteen of these cases were tested for IL-2R, and all were positive (Type I, EMA+, Ki-1+, IL-2R+). In the second group (n = 5), the neoplastic cells expressed EMA but not the Ki-1 antigen. These cases were not tested for the presence of IL-2R (Type II, EMA+, Ki-1-, IL-2R?). There were tumors with similar morphology expressing only Ki-1 antigen (Type III, EMA-, Ki-1+, IL-2R-) or negative for both EMA and Ki-1 antigens (Type IV, EMA-, Ki-1-, IL-2R-). EMA appeared to occur predominantly on activated cells, as has been previously shown for Ki-1 antigen. Analysis using monoclonal antibodies to T-cell, B-cell, or macrophage-associated differentiation antigens showed that these tumors were heterogeneous in terms of cell lineage. Tumors coexpressing EMA, Ki-1, and IL-2R (Type I), were most commonly of T-cell origin (n = 12); the remainder in this type expressed B-cell markers (n = 4), a mixed B/T phenotype (n = 2), or no clear phenotype (n = 9). By contrast, tumors of Types II, III, and IV were mainly from B-cell origin (n = 6) or showed a mixed B/T phenotype (n = 1). Despite the fact that a significant proportion of these cases were initially classified morphologically as "malignant histiocytosis," only 3 of the 63 cases were possibly of histiocytic origin. These results confirm that true malignant histiocytosis is rare and that most tumors with histologic features currently regarded as being consistent with this diagnosis are lymphocytic in origin and express activation antigens such as EMA, Ki-1 antigen, and IL-2R.     

Histopathologic analysis of atypical lesions in image-guided core breast biopsies.

Appropriate follow-up of patients with needle core breast biopsies (NCBB) showing atypical hyperplasia remains unclear because previous studies show that subsequent open biopsies in variable proportions of these patients reveal ductal carcinoma in situ (DCIS) or even invasive carcinoma, indicating significant sampling artifact. NCBB with diagnoses of atypia were morphologically classified into groups as follows: I, ALH (n = 24); II, ADH with minimal cytologic atypism (n = 90); III, atypia, other (9 columnar, 2 apocrine, 11 atypical papillary); IV, severe ADH/borderline DCIS (n = 31). Mammographic and histologic features, including the number of foci of atypia in the NCBB and the calcification span, were then correlated with presence of DCIS or invasive tumor in subsequent open excisions. Open excisional biopsies showed more severe lesions in 12% of Group I-III cases (8% in Group I, 9% in Group II, and 27% in Group III), of which 15 were DCIS and one was an invasive tubular carcinoma (0.3 cm). Of the DCIS, 60% (n = 9) were < or =5 mm, and 13 of 15 (87%) were low grade. The NCBB cavity was immediately adjacent to the more severe lesions in 88% (n = 14) of cases, in keeping with sampling error. The subset showing severe ADH with borderline nuclear features in contrast was associated with a high likelihood (63%) of DCIS in follow-up excisions. NCBB with atypical papillary features also showed a high frequency of DCIS (4/11, 36%) in subsequent open excisions. Other factors associated with more severe lesions on open biopsy included the number of atypical foci in the NCBB (>4, P <.05) and the mammographic calcification span (>2.0 cm, P <.0001). Atypical lesions diagnosed in NCBB samples are radiographically and morphologically heterogeneous, accounting for the variable frequency of DCIS or invasive neoplasm identified in subsequent open excisions, which are usually focal, low grade, and a consequence of sampling artifact (i.e., adjacent to the NCBB cavity). DCIS is more likely if microcalcifications are mammographically extensive or if atypia is multifocal or is associated with borderline cytologic features.     

Gastric phenotypic expression in human gallbladder cancers revealed by pepsinogen immunohistochemistry and mucin histochemistry

Summary Gastric phenotypic expression indicated by paradoxical concanavalin A (Con A) staining for class III mucins and the immunoperoxidase method for pepsinogen (Pg) I and Pg II was found in pyloric gland metaplasia of gallbladder epithelium. Using the same methods, the features of gallbladder cancers and their relationship to pyloric gland metaplasia in the human gallbladder epithelium were studied. Histologically, 57 gallbladder cancers were classified into 5 papillary adenocarcinomas, 29 tubular adenocarcinomas, 8 poorly differentiated adenocarcinomas, 6 signet-ring cell carcinomas, 4 mucinous adenocarcinomas, and 5 squamous cell carcinomas. In papillary and tubular adenocarcinomas, Pg I and/or Pg II staining was detected in 80% and 75.9% of cancers, respectively. Pg II staining was significantly more frequent than Pg I staining. One signetring cell carcinoma also had Pg II activity. Pyloric gland metaplasias all contained class III mucins and were further classified into complete type and incomplete type on the basis of presence or absence Pg I and/ or Pg II activities. A few cancer cells with class III mucins were negative for Pg staining; conversely, a few cells with Pg I and/or Pg II had no class III mucins. Phenotypic diversity in both class III mucin reactivity and Pg activities was observed in gallbladder cancer cells with the pyloric gland cell type. By comparison, pyloric gland metaplasia varied only in Pg activities. A few Pg-positive cancers were found in the gallbladder with Pg-negative pyloric gland metaplasia. The present results clearly indicate the appearance of gastric phenotypic expression in both gallbladder epithelium and gallbladder cancers and suggest the independent induction of pyloric gland metaplasia and cancer with gastric phenotypic expression.     

具有细支气管肺泡癌特征肺腺癌的临床病理分析

目的 进一步了解严格定义的细支气管肺泡癌(BAC)、伴有BAC成分腺癌的比例及预后情况,以及各组织学亚型腺癌的发生率.方法 收集1998-2005年间外科手术治疗病理诊断为肺原发腺癌的病例共348例.按照2004版WHO肺肿瘤分类标准对所有组织学切片进行复习和分类,同时进行临床资料收集,并重点对纯BAC、BAC形态为主伴有局灶浸润的病例、腺癌伴有BAC成分等3组病例进行了随访.结果 纯BAC占腺癌病例的3.7%(13/348),而伴有BAC成分的腺癌则占了31.3%(109/348).大部分切除的肺腺癌都是由不同组织学亚型混合构成,混合亚型所占的比例为78.2%(272/348),混合亚型中的构成成分以腺泡样最为多见(88.2%),其次是BAC(40.1%)、乳头状(24.6%)、实性型(16.9%)等.最少见的构成成分是胎儿型腺癌样结构.对纯BAC病例、BAC形态为主伴有局灶浸润、腺癌伴有BAC成分3组病例的随访发现.前两组患者的生存时间均较长,两者总体生存率没有显著性差异,但是伴有局灶浸润的患者有部分在随访期间出现了进展;而腺癌伴有BAC成分组的病例总体生存率比前两组要差.结论 单纯的BAC、BAC形态为主伴有局灶浸润、腺癌伴有BAC形态的混合亚型具有独特的预后预测作用,而且在临床治疗中对生物靶治疗具有独特反应性,应将其区分开,为临床提供可靠的治疗依据.     

Thymic tumours in Denmark. A retrospective study of 213 cases from 1970-1993.

Histological slides of 213 thymic tumours were reviewed twice and classified according to Kirchner and Müller-Hermelink into 122 thymomas (syn. organotypic thymic epithelial tumours (TET)), 58 thymic carcinomas (syn. non-organotypic TET) and 16 lymphomas. Tumour heterogeneity (i.e. features of two subtypes in one tumour) appeared in 38% of the organotypic TET. The overall diagnostic correspondence between the reviews of the 122 organotypic TET was 48%. By reducing the five diagnostic groups to three: organotypic TET benign (medullary and mixed thymomas), organotypic TET low-grade (organoid and cortical thymomas and well-differentiated thymic carcinoma (WDTC)) and non-organotypic TET (usually high-grade thymic carcinomas), and minimising the effect of tumour heterogeneity in this way, the diagnostic correspondence increased to 82%. Correlating histological type with stage, we found that 80% of medullary and 87% of mixed thymomas were stage I, that 85% of cortical and 81% of WDTC were stage II or III, and that non-organotypic TET were stage II or III (86%) or stage IV (14%), respectively. It is suggested to report on the heterogeneity of a given case of thymic epithelial tumour in the pathology reports and give the approximate percentage of each component, telling the clinician which component may determine the prognosis.     

Relationship between the extent of intraductal component and that of the invasive component in ductal carcinomas of the breast

To clarify the relationship between the extent of the intraductal component and the invasive component in cases of invasive ductal carcinoma (IDC) of the breast, we divided 87 such cases into two groups, Group I in which the intraductal component extended for less than 10 mm (36 cases) and Group II in which the intraductal component extended for 10 mm or more (51 cases). On histological slides, there was an association between the extent of the intraductal component and the pattern of invasion. The majority (80.6%) of Group I IDC cases showed an invasive component composed of one invasive nodule, whereas 62.7% of Group II IDC cases showed an invasive component composed of two or more such nodules. On gross and microscopical examination, Group II IDC showed a significantly larger mean tumor size than Group I IDC (23.4 +/- 8.9 mm vs. 18.3 +/- 6.6 mm, P less than 0.002 & 24.1 +/- 14.1 mm vs. 17.1 +/- 6.5 mm, P less than 0.002). A similar result was obtained by clinical examination (41.8 +/- 17.0 mm vs. 29.5 +/- 11.6 mm, P less than 0.0001). These results suggest that Group II ductal carcinomas may frequently develop multiple stromal invasion, resulting suddenly in a sizeable breast mass perceived by the patient.