Francesco Squartini

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 apocrine 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.

Possible histologic markers for early and late stages of breast cancer.

The degree of productive fibrosis, amount of lymphoid infiltrate and nuclear grade have been studied in 492 consecutive cases of duct-infiltrating breast cancer. It has been found that highly significant relationships exist between these morphologic parameters of breast cancer: lymphoid infiltrate is directly related to nuclear anaplasia and antagonized by productive fibrosis; conversely, productive fibrosis is inversely related to nuclear anaplasia and antagonized by lymphoid infiltrate. Significant inverse relationships between productive fibrosis and lymphoid infiltrate persist in tumors that have the same nuclear grade. It is suggested that lymphoid infiltrate and productive fibrosis are suitable candidates as morphologic markers to estimate the age of breast cancer, while the nuclear grade is a suitable tool to identify subgroups with different behavior in the NOS (not otherwise specified) category of breast cancer.

Quantitative comparison of milk-released C3H and RIII mammary tumor viruses in infected BALB/c hosts.

The C3H and RIII mammary tumor viruses (MTV) carried by BALB/cfC3H and BALB/cfRIII breeding females have been quantified and compared in milk samples, after partial purification with a sucrose density gradient. The samples were collected at identical times during the first 3 lactation periods from individual mice (6 per strain), standardized for age at delivery and size of litter. Milk samples from 6 MTV negative BALB/c controls have also been analyzed. Data for comparison are expressed in optical density units (ODU) and refer to the protein content of the whole milk using MTV-negative BALB/c milk as blank. The results have shown 1) an increase of MTV released through milk in each MTV-carrying female from the first (average ODU, 0.542) to the second (1.351) and third (2.105) lactation, 2) individual variations, and 3) a significant difference in release between C3H and RIIl MTV, the latter being more than double (average ODU, 1.801) in respect to the former (0.847). The apparent discrepancy between these results and the bioactivity in BALB/c mice of C3H and RIII MTV, significantly lower for the latter, is discussed.

Uneven Distribution and Significant Concentration of Apocrine Metaplasia in Lower Breast Quadrants

Two hundred human breasts removed for clinical cancer by radical mastectomy were analyzed to determine whether apocrine metaplasia and apocrine cysts have predilective sites in the four mammary quadrants. One block of tissue randomly removed for each quadrant was examined in one or more histologic sections. The results showed a concentration of apocrine metaplasia and apocrine cysts in the lower mammary quadrants (17.5% versus 8.2%), which is highly significant (x2 = 15.25; P < 0.001). The different distribution between breast cancer (showing predilection for the upper quadrants) and apocrine metaplasia is emphasized, together with the higly significant association between apocrine metaplasia and breast cancer. Based on these data, the usefulness of the clinical detection of cysts in the lower mammary quadrants and needle aspiration of their fluid for the morphologic or biochemical diagnosis of apocrine metaplasia in the screening and management of women at risk is suggested.

Relationships between morphology and viral etiology in mammary tumors of BALB/cfC3H and BALB/cfRIII mice.

The morphologic patterns of mammary tumors induced by milk-transmitted C3H and RIII murine mammary tumor viruses (MuMTVs) in BALB/c hosts infected by foster nursing were investigated further and compared taking into account several tumor and host variables. Comparison of BALB/cfC3H and BALB/cfRIII mammary tumors under identical tumor and host conditions showed highly significant differences in subgross morphology and histologic structure. Differences in cytology were also observed. Data suggest that mammary tumor morphology in high cancer strain mice is controlled by the causative MuMTV.

Relationship of the degree and type of intraductal component with other morphologic findings in breast cancer.

The presence of mammary lobules around overt cancer and the amount and the type of intraductal tumor component (solid, comedo, cribrous, comedo-cribrous, papillary) were defined in 493 consecutive cases of infiltrating human breast cancer to analyze the association of these parameters with other morphologic parameters, such as productive fibrosis, lymphoid infiltrate and nuclear grade. Data showed a significant inverse relationship between degree of intraductal component and productive fibrosis (p < 0.01) and direct relationships between a) presence of lobules and degree of intraductal component (p < 0.02) and b) intraductal component of comedo type and lymphoid infiltrate (p < 0.02). In addition, marked though not significant associations were observed between a) absence of lobules and intraductal component of papillary type (p < 0.10) and b) nuclear grade 1 and intraductal component of the comedo type (p < 0.10). Data suggest that cancers with a high degree of introductal component could have a lobular origin and papillary cancer could have a ductal origin. The other relationships observed might be useful in the subclassification of NOS (not otherwise specified) breast cancer.

Characteristics of lymphomas in the BALB/cfRIII mouse strain.

The occurrence of 392 lymphomas in 1607 BALB/cfRIII mice from F0 to F45 is analyzed. Lymphoma incidence increased rapidly in the first 5 generations, reached a high plateau from F6 to F20 and then decreased slowly until it disappeared altogether. After F85, only sporadic cases of lymphoma have been observed. The morphologic characteristics of 350 of these lymphomas observed from F0 to F20 are described. Three main types of lymphomas have been recognized on the basis of gross morphology, histology and age: a) early, lymphocytic, with thymic involvement; b) early, lymphocytic, without thymic involvement; and c) late, histiocytic, without thymic involvement. The first 2 types are virus-induced and thymus-dependent, and the third type is both virus and thymus independent. Lymphomas without thymic involvement and histiocytic lymphomas increased with the generations. The source of causative virus, the interference with mammary tumors, and the possible cell types of origin of lymphomas are discussed.