Fatal peripheral airway cystic disease in a young woman.

Diffuse cystic transformation of both lungs was rapidly fatal in a 33-year-old woman. This disorder, a rare congenital condition in infants, has apparently not been described in adulthood.

Comparison of monoclonal immunocytochemical and immunoenzymatic methods for steroid receptor evaluation in breast cancer.

The production of monoclonal antibodies against estrogen receptor (ER) and progesterone receptor (PR) has permitted the development of the enzyme immunoassay (EIA) and immunocytochemical assay (ICA) for steroid receptor determination. The results obtained with these two techniques, using the same monoclonal antibodies, were compared in a large series of breast carcinomas (187 for ER and 100 for PR). The correlation between these methods was significant for ER (rs = 0.54) and PR (rs = 0.55) (P less than 0.001) but was lost when the receptor concentrations determined by EIA were less than or equal to 15 and less than or equal to 30 fmol/mg protein for ER and PR, respectively. When these values are considered as cutoffs, the concordance between the two methods was 84.5% for ER and 73% for PR. An analysis of discordant results revealed that low epithelial cellularity generally was present in ICA-positive, EIA-negative specimens, whereas only focal positivity with ICA, or positivity of only normal peripheral mammary ducts and lobules, frequently was found in ICA-negative, EIA-positive tumors. In conclusion, there is good correlation between the results obtained by EIA and ICA methods for detection of ER and PR. The authors suggest that biochemical and histochemical methods for steroid receptors could be considered complementary and used together for the analysis of breast cancer.

Estrogen, progesterone receptors and proliferating activity evaluated by immunocytochemistry in breast cancer.

The correlation of the most important prognostic indicators was evaluated in 75 breast cancer cases. Estrogen-progesterone receptors and proliferating activity were analyzed by immunocytochemical methods (ER-ICA, PR-ICA, Ki-67). Both steroid receptors were inversely correlated with the proliferating activity (ER-ICA vs Ki-67, p less than 0.003; PR-ICA vs. Ki-67, p less than 0.0001). No correlation was found between steroid receptors or cell kinetics and tumor size or lymph node status. These findings confirm the relevance of biochemical and kinetic parameters as independent markers in breast cancer and suggest a routine use of the simple immunocytochemical methods in assessing the biological behavior of tumors.

Frequency-dependent attenuation in breast tissue characterization.

The aim of this study is to establish whether an index derived from the slope of the frequency-dependent ultrasonic attenuation can provide quantitative information on normal and pathological breast tissue. Ultrasonic measurements were performed by using pulsed transmitted ultrasound in the frequency range 2-8 MHz. Thirty-three specimens were selected for their probable pathologic classification, by macroscopic observation, before ultrasonic study, and subsequently histologically classified. Ultrasonic results suggest the possibility that the examined specimens fall into four groups: (1) fat, fibroadenoma, giant fibroadenoma, infiltrating ductal carcinoma, medullary carcinoma; (2) infiltrating lobular carcinoma, tubular carcinoma, scirrhous carcinoma; (3) fibrosis; (4) fibrofatty tissue, fibrocystic disease. Correlative morphological studies indicate that the employed index can classify breast tissues on the basis of their cellular and fibrous composition and the inhomogeneity of their structure.

Evaluation of frequency dependence of backscatter coefficient in normal and atherosclerotic aortic walls.

For five groups of aortic specimens (normals and with different degrees of atherosclerosis) the ultrasonic backscatter coefficient was measured as a function of frequency in the range 4-15 MHz. The results of the study are related to two classes of structure, connective and fatty tissue (whose relative amount in the arterial wall is related to the different stages of atherosclerosis), as the main determinants of the scattering from aorta. The structure of connective tissue in the aorta produces a power law frequency dependence of the backscatter coefficient typical of small scale structures (Ka much less than 1). Fatty tissue introduces a frequency dependence of the backscatter coefficient typical of structures of intermediate scale (Ka approximately equal to 1). Biochemical composition and structure of normal and atherosclerotic aorta therefore, specifically affect the employed acoustical parameter.

Orientation and frequency dependence of backscatter coefficient in normal and pathological breast tissues.

The backscatter coefficient was measured on five groups of normal and pathological breast specimens: (1) as a function of frequency (in the range 4-14 MHz) and (2) at a single fixed frequency (10 MHz), as a function of the angle of incidence between the beam and the specimen (approximately 60 degrees). The results of the study are discussed in relation to the content of cells and collagen fibers in breast tissues. The absolute value of backscatter coefficient is larger in tissues with a prevalence of collagenous fibers in comparison to tissues with only cells. In fibrofatty tissue, the inhomogeneity of the specimens is probably responsible for the highest backscatter value. The power law frequency dependence of the backscatter coefficient is of a diffractive nature in tissues characterized by only cells; in tissues with a strong prevalence of collagenous fibers, the power law frequency dependence increases. Periodicities in the angular patterns have been quantified by the autocorrelation functions for each group of specimens. The results of the study suggest a means for assessing tissue structure in normal and pathological breast tissue.

Gallbladder carcinoma: a video image analysis of AgNOR distribution and its relation to tumour stage and grade.

The amount and distribution of interphase argyrophilic nucleolar organizer regions (AgNORs) was studied in 51 gallbladder surgical specimens including 32 primary carcinomas, 10 adenomas and 9 cases of chronic cholecystitis with calculi. The mean nuclear AgNOR area (NORA) and the AgNOR distribution score (NORDS), i.e. the percentage of cells carrying nucleolar aggregates with more than 6 distinct silver dots, were evaluated in 200 epithelial nuclei per specimen by means of automated image analysis and direct counting respectively. Statistical analysis (variance analysis and Student-Neuman-Keuls' test) performed on the pooled mean AgNOR values showed a significant difference (p < 0.001) between carcinomas and non-carcinomatous lesions. Both NORA and NORDS highly discriminated carcinomas with histopathological grade 4 versus cases with grade 1, 2 or 3 (p < 0.001); a less statistically significative p value (< 0.05) was encountered when NORDS values of well differentiated grade 1 carcinomas and adenomas were compared. The NORA parameter permitted the discrimination of stage IV versus stage I carcinomas (p < 0.001), while carcinomas in stage IV and those in stage II were distinguished with a p < 0.05; the NORDS parameter allowed also to distinguish stage IV from both stage I or II tumours (p < 0.001). Our results indicate that the above-mentioned AgNOR parameters may be utilized as additional, more objective quantitative criteria in the clinical-pathological assessment of the outcome of gallbladder carcinomas.

Differences in AgNOR quantity between colorectal cancer and corresponding metastases: are they useful for prognostic purposes?

In order to evaluate the relationship between primary colorectal adenocarcinomas and their metastases with regard to AgNOR proteins expression, we have performed a morphometric analysis of AgNOR silver precipitates (AgNORs) in advanced colorectal carcinomas (stage III-IV) as well as in corresponding lymph node and distant metastases. Surgical specimens studied consisted of 64 primary tumours, 56 lymph node and 43 hepatic or omental metastases; for each formalin-fixed paraffin-embedded specimen, silver staining according Ploton et al. (1986) was performed and the AgNOR area (NORA) relative to primary site, lymph node and/or distant metastases was calculated. A significant difference (P < 0.001) among the non-neoplastic colonic control mucosae and primary or metastatic neoplastic lesions was found, but no statistically significant differences were encountered among the categories of primary colorectal carcinomas and their lymph node or distant metastases. Moreover, on the basis of NORA data case per case, three groups of patients were selected. In particular, in the group 1 NORA values of metastases were higher than those of the corresponding primary carcinomas, while in the group 2, NORA values of metastases were lower than those of the corresponding primary neoplasms; no differences of NORA values were encountered in group 3. The cumulative patient survival estimated by the Kaplan-Meier method showed a worse prognosis for patients belonging to group 1, where higher AgNOR values, not only in primary carcinomas but also in lymph node and distant metastases, were found.

Independent submacroscopic foci of infiltrating carcinoma in breasts removed for clinical cancer.

The aim of our study was the detection and the characterization of submacroscopic foci of infiltrating carcinoma in the human female mammary glandular tree collateral to clinical cancer. Accordingly, we analyzed 100 breasts surgically removed by radical mastectomy. Five thin slices per case were analyzed under a dissecting microscope by subgross method of observation. Submacroscopic foci of invasive cancer, well separated and apparently independent of the primary tumor, were found in 19% of the cases and were confirmed by histologic examination. Foci of submacroscopic cancer were either single (79%) or multiple (21%), and were located in slices including or not the main tumor mass (31% and 69% of cases, respectively). Their size ranged from 1 to 4 mm. Four histologic types were represented: 1) invasive ductal NOS with productive fibrosis, scirrhous type (36% of cases); 2) invasive ductal NOS without productive fibrosis, simplex type (32% of cases); 3) invasive ductal with tubular component (16% of cases); 4) medullary (16% of cases). Concordance between histology of clinical and submacroscopic cancers was assessed in 42% of cases. A significant association of the tubular type (invasive ductal carcinoma with a consistent tubular component) of primary tumor was demonstrated (P less than 0.05), as well as with the presence of ductal and lobular proliferative changes in the collateral glandular tree (intraductal papillomas, P less than 0.01; atypical lobules, P less than 0.02). No relationship was found between submacroscopic foci of infiltrating carcinoma and neoplastic familiarity, patients' age by decades, axillary lymph node metastases, size of clinical tumor or profile of the collateral mammary glandular tree. These data support the hypothesis of a multicentric origin of human breast cancer and suggest a systemic nature of the neoplastic mammary disease. Prognostic and therapeutic implications of this concept are discussed.

Subgross physiopathology of the breast associated with clinical cancer.

Fifty human breasts removed for cancer by radical mastectomy were submitted to subgross analysis of the glandular tree as a whole, stained thin sections (2 mm) under a dissection microscope, followed by histologic study of the lesions found. The glandular tree was more often atrophic (70%) than hyperplastic (30%). The frequencies of physiopathologic changes were as follows: ductal papilloma (4%), ductal hyperplasia (6%), fibroadenoma (16%), sclerosing adenosis (24%), cysts (28%), apocrine cysts (18%), cystic ducts (40%), blind terminal ducts (60%), atrophic lobules (88%), sclerotic lobules (34%), hyperplastic lobules (28%), cystic lobules (52%), persistent lobules in otherwise atrophic breasts (30%), lobules with aporcine metaplasia (30%), atypical lobules with proliferative changes (38%), and independent foci of microscopic cancer (20%). The data indicate: 1) a frequent lack of correlation between ovarian function (menstrual cycles, menopause) and type of mammary glandular tree (hyperplastic, atrophic); 2) a rarity of ductal lesions compared with the frequency of lobular lesions; 3) a ubiquitous distribution of the lesions either near or far from clinical cancer; 4) a significant association of atypical lobules with lobular sclerosis (p < 0.001) and apocrine metaplasia (p < 0.05). The frequency and ubiquity of lobular changes suggest further investigation among them to search for suitable candidates as preneoplastic or predictive lesions.

The prevalence of the precancerous lesions in breasts contralateral to clinical cancer. A morphological comparison with breasts containing a benign lump.

Two small series (nine cases each) of human female breasts were collected to compare the morphological changes of mammary glandular trees contralateral to primary breast cancer and those collateral to symptomatic benign lump. Each whole mammary gland was analysed by a submacroscopic scrutiny method using a stereomicroscope. Interesting and suspicious samples were removed for routine histology. Benign subclinical lesions were indifferently present in both series: Spheric cysts (5:5), sclerosing adenosis (3:3), intraductal papillomas (1:1), fibroadenomas (3:1). On the contrary proliferative epithelial lobular lesions with various degree of atypia i.e. atypical lobules (Grades IV-V according to Wellings), were detected only in the first series (p < 0.01). These data agree completely with the hypothesis of a systemic nature of breast cancer and support indirectly the possible predictive value of atypical lobules in bioptic specimens for the subsequent development of cancer in collateral and/or contralateral breasts.

Fibrocystic condition and "at risk" lesions in asymptomatic breasts: a morphologic study of postmenopausal women.

A series of postmenopausal women who had died without noticing any clinical breast disease in their anamnesis (100 cases, age range 46-90 years, average age 62 years) were submitted to bilateral subcutaneous mastectomy during autopsy in order to evaluate the morphologic profile of asymptomatic mammary glands, at different ages. Submacroscopic changes were found and removed to be processed for histology. Results were as follows: a) 46% of cases did not show any change; b) 54% of cases showed benign changes, namely a fibrocystic condition; c) 14% of cases had in addition epithelial lobular hyperplasia with low grade atypia and d) 3% of cases showed atypical borderline lobules (ABL), i.e., terminal ductal-lobular units characterized by severe epithelial atypia. Such lesions cannot be easily distinguished from "in situ" carcinoma, and are currently considered at morphologic risk for subsequent cancer when found in breast biopsies. Our data show that: 1) ABL do not represent a common finding in women who never complained of breast pathology during life; 2) ABL are not related to older age; 3) Fibrocystic condition is quite frequent at subclinical levels also in asymptomatic aging women. The latter statement confirms the opinion that fibrocystic condition should be considered as a common "functional" change. On the contrary, the rarity of ABL gives us a further indirect evidence of their possible precancerous significance. The risk of subsequent development of cancer from the collateral mammary gland could be theoretically higher when ABL are found in breast biopsies of fertile and premenopausal women, who have a longer period of life expectation.

Ganglioglioma of the spinal cord. A case with a long survival.

A case of ganglioglioma or neuroastrocytoma of the spinal cord in a 78-year-old man is reported. Diagnosis was based on the histological identification of the neoplastic cells and on the study of the architecture of the tumour. The presence of cellular anaplasia, sometimes of marked degree, and of small nests of infiltration suggested an initial malignant behaviour regarding both cellular types. A survey of the five reported cases of spinal ganglioglioma is presented.

Multicentricity in breast cancer: a submacroscopic study.

One hundred human female breasts surgically removed by radical mastectomy for clinical cancer were analyzed under a dissecting microscope to search for other submacroscopic (less than 0.5 cm) foci collateral to and independent from the clinical one. These foci were found in 36 percent of cases, either in situ (17 percent), or infiltrating (12 percent), or both in situ and infiltrating (7 percent). This high percentage of multiple cancer confirms previous data, suggesting the wide intramammary distribution of breast cancer disease. Multicentricity appears to be significantly associated with the incidence of familial breast cancer (p less than 0.05) and advanced patient age in the range between 71 and 80 years (p less than 0.005). Axillary lymph node metastases are significantly associated with collateral foci of in situ cancer (p less than 0.025), but not with submacroscopic foci of infiltrating cancer and the general character of the mammary glandular parenchyma, tumor size or histologic type of the clinical neoplasm. The critical question is whether multicentricity makes a difference clinically and especially to women who do not have their entire breast removed. Radical mastectomy results in a severe cosmetic and functional problem for patients. According to many authors, the goal of the treatment should be the removal of breast cancer by conservative surgical techniques (lumpectomy, subcutaneous mastectomy, quadrantectomy), using adjuvant radiotherapy and/or chemotherapy. The use of radiotherapy as primary treatment of early breast cancer has been also suggested. There is disagreement about surgical management of breast cancer. In fact, some investigators emphasize that the natural biologic history of multicentric cancers has not been documented by any adequate follow-up series in women who do not have their entire breast removed. Thus far, no difference has been seen in disease-free or overall survival between groups of patients with early breast cancer treated by an alternative therapeutic procedure and patients treated by radical mastectomy. However, Veronesi et al. (1981) refer to 4 second primary tumors of the ipsilateral breast in the 352 cases of small cancers treated by quadrantectomy, axillary dissection, and adjuvant radiotherapy. Moreover, Hellman et al. (1980), using radiation therapy without mastectomy for the primary treatment of 176 patients with early breast cancer, found 1 case of new cancer in a separate quadrant. Further evaluation is necessary to establish the long-term results of the alternative treatments of breast cancer and for the understanding of the clinical significance of microscopic multifocal tumor in the mammary gland.

Correlations between histologic type of clinical breast cancer and physiopathologic profile of the mammary glandular tree.

The relationships between cancer histotype and characters of the mammary glandular tree have been studied in 100 human breasts removed for clinical cancer by radical mastectomy. The group of invasive ductal carcinomas, including 78 cases, was subclassified in not otherwise specified (53 cases), with intraductal (19 cases), and with tubular component (6 cases). The other cancer histotypes were invasive lobular carcinoma (9 cases), medullary carcinoma (7 cases), mucinous carcinoma (4 cases), and papillary carcinoma (2 cases). The pattern of the mammary glandular tree was atrophic (67 cases) or adenosic, i.e., rich in mammary lobules (33 cases), but mammary lobules (normal, paranormal, atypical, or persistent in otherwise atrophic breasts) were present in 83% of the cases. A significant prevalence of not otherwise specified cancer (X2 = 10.20; p less than 0.01) was found in atrophic breasts (64%) and, even more, in breasts without lobules (76%). By contrast, intraductal component, tubular component, invasive lobular, and medullary cancers were, with two single exceptions, only in breasts with lobules, and this concentration was also significant (X2 = 7.26; p less than 0.01). It is concluded that breast cancer histotype is influenced by, or related to, the surrounding microenvironment, i.e., the pattern of the mammary glandular tree.

The microenvironment of human breast with clinical cancer.

The characteristics of the mammary glandular tree have been studied in 100 human breasts removed for clinical cancer by radical mastectomy. The glandular tree was observed in whole thin (2 mm) stained sections under a stereoscopic microscope with removal of any suspicious or interesting change for histology. The results allow to categorize as follows the microenvironments in which mammary neoplasia may clinically appear. In respect to the main characteristics of the collateral glandular tree, clinical breast cancer may occur in: (a) atrophic breasts without lobules or lesions in 17% of cases; (b) atrophic breasts with persistent lobules and minor pathologic changes such as cysts, apocrine metaplasia, sclerosing adenosis, fibroadenoma and ductal hyperplasia in 19% of cases; (c) atrophic breasts with proliferative lobular changes (atypical lobules), duct papillomas, in situ carcinomas and/or microscopic independent foci of infiltrating carcinoma in 31% of cases; (d) adenosic breasts, which are breasts rich in mammary lobules, with the minor pathologic changes specified under (b) in 14% of cases; (e) adenosic breasts with the severe proliferative changes specified under (c) in 17% of cases, and (f) adenosic breasts with normal lobules and without lesions in 2% of cases. Therefore, 83% of the cancerous breasts have normal or pathologic lobules and 81% have lesions of various degrees of severity in the glandular tree.