Skin diseases of the breast and nipple: Benign and malignant tumors.

The evaluation and management of dermatologic diseases of the breast and nipple requires an understanding of the unique anatomy of the breast and nipple and an awareness of the significant emotional, cultural, and sexual considerations that may come into play when treating this anatomic area. The first article in this continuing medical education series reviews breast anatomy, congenital breast anomalies, and benign and malignant breast tumors. An emphasis is placed on inflammatory breast cancer and breast cancer with noninflammatory skin involvement and on cutaneous metastases to the breast and from breast cancer. Familiarity of the dermatologist with the cutaneous manifestations of breast cancer will facilitate the diagnosis of breast malignancy and assist with staging, prognostication, and evaluation for recurrence. This article also discusses genodermatoses that predispose to breast pathology and provides imaging recommendations for evaluating a palpable breast mass.

Chemokine C-C motif ligand 18 expression correlates with tumor malignancy in breast cancer.

PURPOSE OF THE STUDY: To investigate whether CCL18 is involved in breast cancer, and the relationship between CCL18 and MVD (MVD was recognized by CD34) which is a well-accepted angiogenic maker of multiple cancers including breast cancer. PATIENTS AND METHODS: Immunohistochemistry staining for CCL18 and CD34 was performed on 179 cases, including 29 normal cases as control, 47 cases with benign breast diseases, and 103 cases with breast cancer. RESULTS: We found that CCL18 was significantly up-regulated in breast cancer samples as compared with benign tumors or normal breast tissues. Moreover, the expression level of CCL18 increased with the size of tumors, the number of lymph node metastasis, and advancing tumor stage, suggesting that CCL18 expression correlates with tumor malignancy scales. At the same time, we found that MVD was also significantly over-expressed in cancer tissues as compared with normal control group and benign tumor group, but it was not significantly differentially expressed among tumors with different malignancy scale like CCL18, while the expression of MVD in CCL18 positive breast cancer cases was higher than in the CCL18 negative breast cancer cases (P=0.016, P<0.05). CONCLUSION: CCL18 is involved in the development of breast cancer. CCL18 is a better biomarker than MVD in determining whether the tumor is malignant and the severity of malignancy of breast cancer.

Mouse TBX3 mutants suggest novel molecular mechanisms for Ulnar-mammary syndrome.

The transcription factor TBX3 plays critical roles in development and TBX3 mutations in humans cause Ulnar-mammary syndrome. Efforts to understand how altered TBX3 dosage and function disrupt the development of numerous structures have been hampered by embryonic lethality of mice bearing presumed null alleles. We generated a novel conditional null allele of Tbx3: after Cre-mediated recombination, no mRNA or protein is detectable. In contrast, a putative null allele in which exons 1-3 are deleted produces a truncated protein that is abnormally located in the cytoplasm. Heterozygotes and homozygotes for this allele have different phenotypes than their counterparts bearing a true null allele. Our observations with these alleles in mice, and the different types of TBX3 mutations observed in human ulnar-mammary syndrome, suggest that not all mutations observed in humans generate functionally null alleles. The possibility that mechanisms in addition to TBX3 haploinsufficiency may cause UMS or other malformations merits investigation in the human UMS population.

Tuberous breast: revised classification and a new hypothesis for its development.

The tuberous breast classification proposed by Grolleau does not account for a minor form of the deformity characterized by isolated nipple-areola protrusion with a normal breast base. We have observed this minor form in six patients with normal breast shape and in ten patients with hypertrophic breasts. We propose an anatomical and physiological hypothesis for the development of the mammary gland. The breast is subjected to hormonal influences as early as the prepubertal period. These influences result in thrusting forces with both horizontal (estrogen) and vertical (progesterone) vectors, unfortunately not always balanced and harmonious. Close observation of the anomaly in our patients substantiated the basic anatomical defect, namely, the structural congenital dermal weakness of the nipple-areola complex (NAC) already described in all forms of tuberous breast deformity. This weakness explains the morphologic anomaly and confirms that all types of tuberous breast deformity constitute a spectrum of a single entity. It indicates also that the classification of tuberous breasts should include, in addition to the three types (types I-III) already described, a fourth type (type 0) to describe isolated simple areola protrusion, either permanent or intermittent, that is associated with a normal mammary base. The revised classification of tuberous breasts and the proposed hypothesis of breast development allow better assessment of all possible variants of breast morphologic anomalies. In the six cases of isolated herniated NAC, the deformity was corrected through a perinipple approach (not circumareolar), with adequate stable correction of the deformity and minimal scarring.

Breast diseases in adolescents.

Fibroadenomas and breast growth disorders are the most common breast diseases in adolescent women. Assessment of breast disorders in this age group generally involves clinical evaluation through history and physical examination and when is needed ultrasonography. Due to the absence of breast cancer in adolescent women, it is easy to reassure women at the first consultation. Breast growth disorders can lead great psychological and physical embarrassment. Treatment consists of surgical procedures when the cosmetic defect is severe. According to the ANDI classification, small fibroadenomas are normal, clinical fibroadenomas are a mild aberration of the normal processes, and giant or multiple fibroadenomas are placed to the disease end of the spectrum. Fibroadenomas can be treated conservatively provided diagnosis is confident. Giant fibroadenomas are treated by surgical enucleation. Breast abscess is mainly due to the duct ectasia. In adolescence, ectasia has been described as an exaggeration of sinus duct development and can be considered as a variant of normality. Diseases of the adolescent breast are usually benign and their management are simple using medical strategy and more rarely surgical therapy.

Breast disorders in children and adolescents.

A review of pediatric breast disorders is provided, with particular attention given to the topics of fibroadenoma, cystosarcoma phylloides, breast infections, breast cancer, and benign breast disease. The pediatric clinician is strongly encouraged to include the breast system as part of a complete examination and educational process.