Giant lactating adenoma

Lactating adenoma is a rare benign breast lesion that most often presents as a small (up to 3 cm), solid, well-circumscribed, solitary, painless, mobile, lobulated mass. The highest incidence occurs in primiparous women (20 to 40 years old) during the third trimester of pregnancy. However, in the rare case presented herein, in addition to its giant size (more than 10 centimeters on palpation), this lactating adenoma is distinctive due to the presence of multiple nodules, poorly defined ultrasonographic margins, worrisome radiologic features, growth since early pregnancy, presence of infarction and association with chronic mastitis. From the clinical-radiologic perspective, the differential diagnoses included abscess associated with puerperal mastitis, phyllodes tumor, and galactocele. Biopsy was performed, and pathologic examination revealed the classic characteristics of lactating adenoma with multiple infarcted areas, leading to an unexpected confirmed case of giant lactating adenoma.

ABM Clinical Protocol #32: Management of Hyperlactation.

A central goal of the Academy of Breastfeeding Medicine is the development of clinical protocols for managing common medical problems that may impact breastfeeding success. These protocols serve only as guidelines for the care of breast-feeding mothers and infants and do not delineate an exclusive course of treatment or serve as standards of medical care. Variations in treatment may be appropriate according to the needs of an individual patient.

Preeclampsia-Like Features and Partial Lactation Failure in Mice Lacking Cystathionine γ-Lyase-An Animal Model of Cystathioninuria.

Elevated plasma homocysteine levels are considered as a risk factor for cardiovascular diseases as well as preeclampsia-a pregnancy disorder characterized by hypertension and proteinuria. We previously generated mice lacking cystathionine γ-lyase (Cth) as cystathioninuria models and found them to be with cystathioninemia/homocysteinemia. We investigated whether Cth-deficient (Cth-/-) pregnant mice display any features of preeclampsia. Cth-/- females developed normally but showed mild hypertension (~10 mmHg systolic blood pressure elevation) in late pregnancy and mild proteinuria throughout development/pregnancy. Cth-/- dams had normal numbers of pups and exhibited normal maternal behavior except slightly lower breastfeeding activity. However, half of them could not raise their pups owing to defective lactation; they could produce/store the first milk in their mammary glands but not often provide milk to their pups after the first ejection. The serum oxytocin levels and oxytocin receptor expression in the mammary glands were comparable between wild-type and Cth-/- dams, but the contraction responses of mammary gland myoepithelial cells to oxytocin were significantly lower in Cth-/- dams. The contraction responses to oxytocin were lower in uteruses isolated from Cth-/- mice. Our results suggest that elevated homocysteine or other unknown factors in preeclampsia-like Cth-/- dams interfere with oxytocin that regulates milk ejection reflex.

Trpc5 deficiency causes hypoprolactinemia and altered function of oscillatory dopamine neurons in the arcuate nucleus.

Dopamine neurons of the hypothalamic arcuate nucleus (ARC) tonically inhibit the release of the protein hormone prolactin from lactotropic cells in the anterior pituitary gland and thus play a central role in prolactin homeostasis of the body. Prolactin, in turn, orchestrates numerous important biological functions such as maternal behavior, reproduction, and sexual arousal. Here, we identify the canonical transient receptor potential channel Trpc5 as an essential requirement for normal function of dopamine ARC neurons and prolactin homeostasis. By analyzing female mice carrying targeted mutations in the Trpc5 gene including a conditional Trpc5 deletion, we show that Trpc5 is required for maintaining highly stereotyped infraslow membrane potential oscillations of dopamine ARC neurons. Trpc5 is also required for eliciting prolactin-evoked tonic plateau potentials in these neurons that are part of a regulatory feedback circuit. Trpc5 mutant females show severe prolactin deficiency or hypoprolactinemia that is associated with irregular reproductive cyclicity, gonadotropin imbalance, and impaired reproductive capabilities. These results reveal a previously unknown role for the cation channel Trpc5 in prolactin homeostasis of female mice and provide strategies to explore the genetic basis of reproductive disorders and other malfunctions associated with defective prolactin regulation in humans.

mTOR Inhibition Subdues Milk Disorder Caused by Maternal VLDLR Loss.

It is unknown whether and how very-low density lipoprotein receptors (VLDLRs) impact skeletal homeostasis. Here, we report that maternal and offspring VLDLRs play opposite roles in osteoclastogenesis and bone resorption. VLDLR deletion in the offspring augments osteoclast differentiation by enhancing RANKL signaling, leading to osteoporosis. In contrast, VLDLR deletion in the mother alters milk metabolism, which inhibits osteoclast differentiation and causes osteopetrosis in the offspring. The maternal effects are dominant. VLDLR-null lactating mammary gland exhibits higher mTORC1 signaling and cholesterol biosynthesis. Pharmacological probing reveals that rapamycin, but not statin, treatment of the VLDLR-null mother can prevent both the low bone resorption and our previously described inflammatory fur loss in their offspring. Genetic rescue reveals that maternal mTORC1 attenuation in adipocytes, but not in myeloid cells, prevents offspring osteopetrosis and fur loss. Our studies uncover functions of VLDLR and mTORC1 in lactation and osteoclastogenesis, illuminating key mechanisms and therapeutic insights for bone and metabolic diseases.

Rusty pipe syndrome, a cause of bloody nipple discharge: case report.

Breastfeeding has universally known advantages to the mother and child that include nutritional and immunological benefits but also involve reasons of ecological and economic order. Initiation and maintenance of breastfeeding can be associated with common problems. The beginning of milk production may course with bloody nipple discharge, which, after exclusion of pathological entities, concerns a self-resolving physiological syndrome called rusty pipe. We present a case of rusty pipe syndrome and discuss the implications.

Milk flow obstruction caused by varicose vein of the teat in dairy cattle.

OBJECTIVE: To describe varicose vein as a cause of obstruction of the teat cistern in dairy cattle and to report therapeutic options and outcome. STUDY DESIGN: Retrospective case series. ANIMALS: Dairy cows (n = 22). METHODS: Medical records (1998-2011) of dairy cows admitted for milking difficulties caused by a teat varicose vein were reviewed. Three treatment approaches were used: sclerotherapy, ligation of the vein associated with sclerotherapy, and phlebectomy. Long-term outcome was obtained ≥ 6 months after treatment and defined as a milking improvement. Descriptive statistics were used to determine the population at risk and a chi square test was used to evaluate the relationship between treatments and outcomes. RESULTS: Twenty-four teats (22 cows) had a varicose vein. Forequarters were more frequently affected than rear quarters (P < .01). Three sclerotherapies, 12 ligations associated with sclerotherapy and 6 phlebectomies were performed. Five veins were not treated. Overall prognosis with treatment was good (84%) at ≥ 6 months and was not significantly different between treatment types (P = .38). Recurrence of the obstruction by the varicose vein occurred in 3 of 19 teats. CONCLUSIONS AND CLINICAL RELEVANCE: Several surgical options are available for treatment of teat varicose veins. The overall prognosis of return to normal milking is good.

Xanthogranulomatous reaction to a ruptured galactocele.

We describe a case of a 34-year-old, healthy, lactating female with a 2-month history of breast pain and an enlarging, tender mass on her right nipple. Her right breast was firm and mildly engorged without mass, warmth or erythema. A tender, yellow nodule was located on the superior aspect of the nipple, obstructing the flow of milk from this portion of the nipple. A biopsy showed epidermal erosion, sheets of cells with massively distended, foamy cytoplasm in the dermis, and a hypertrophied and occluded glandular duct, consistent with reactive squamous metaplasia. Immunostaining for CD68 confirmed the foamy cells were macrophages, and anti-human milk fat globulin-1 (HMFG1) labeled the substance within the macrophages consistent with human breast milk. Therefore, the lesion could be identified as a xanthogranulomatous reaction to a ruptured galactocele.

Classification of inflammatory breast disorders and step by step diagnosis.

In this study, the authors proposed a classification of inflammatory breast disorders based on which a practical systematic scheme in diagnosis was applied aiming to differentiate simple forms of mastitis from more complicated and malignant forms. The study population included 197 female patients who were clinically or pathologically diagnosed as having mastitis. All patients underwent Ultrasound examination. Mammography was performed for 133/197 cases. Cases of simple mastitis and periductal mastitis were followed up to ensure complete resolution. Abscess cavities and postoperative collections were drained. Other cases were biopsied to confirm diagnosis and were managed accordingly by their treating physicians. Statistical analysis was performed by the Statistical Package for Social Science. Nominal Data were expressed as frequency and relative frequencies (percentage). Ultrasound and Mammography categorical results were compared using the Pearson Chi Square and Fisher's exact test. Patients were classified into three groups; infectious, noninfectious and malignant mastitis. Simple and malignant forms of mastitis showed many signs in common. The presence of ill defined collections and abscess cavities on ultrasound favored simple over malignant forms of mastitis while extensive skin thickening and infiltrated malignant nodes favored malignant forms. Interstitial edema, edematous fat lobules, abscess cavities, skin thickening seen on ultrasound examination were significantly lower in noninfectious than simple and malignant mastitis. Mammography signs were less discriminating. Diffuse skin thickening and increased density favored malignant mastitis while dilated retro areolar ducts and characteristic calcification patterns favored noninfectious forms. Simple mastitis showed nonspecific signs. Ultrasound examination in mastitis cases shows more specific signs in differentiating between the three forms of mastitis and is useful in monitoring treatment, excluding complications and guide for interventional procedures. Mammography should be performed whenever complicated, malignant and uncommon forms of mastitis are suspected.

Incontinentia lactis: physiology and anatomy conducive to milk leakage in dairy cows.

Incontinentia lactis is a possible predisposing factor for an elevated level of intramammary infection. The goal of the present study was to investigate possible causes of incontinentia lactis in dairy cows. Two farms that differed in breed composition, but that had similar average milk yields were studied: herd A, 28 kg/d, 31 Red Holstein cows; and herd B, 26 kg/d, 16 Brown Swiss cows. Herd A was classified into 2 groups: incontinentia lactis (ILA group) and control, whereas herd B was exclusively a control herd. Milk samples that represented foremilk and the main milk fraction were collected during 4 milking sessions. In addition, milk leakage samples from the ILA group were collected at different time intervals from 0 to 5 h before milking. Measurements of the teat, milk flow, fractions of cisternal and alveolar milk, intramammary pressure, and blood oxytocin pattern also were obtained. The ILA cows did not have differences in fat content between milk leakage and cisternal milk fraction. Milk fat content, however, increased during milking in response to continuous milk ejection (1.95, 1.99, and 4.61% for milk leakage, cisternal, and main milk samples, respectively). Teat canals were 9% shorter in the ILA cows, which showed greater milk yield, peak, and average flow rates. Quarter cisternal milk yield of ILA cows tended to be greater (0.50 vs. 0.23 and 0.28 kg for ILA and controls from herds A and B, respectively), whereas percentages of cistern milk and alveolar milk did not differ from controls. The greater pressure in the ILA group, both before and after manual udder stimulation (ILA: 4.0 and 6.4 kPa; control: 2.0 and 5.0 kPa, respectively), could be an important cause for the leakage. Nevertheless, the increase in IMP that occurred after udder preparation affirms that milk ejection occurred in response to the tactile teat stimulation, but not before the onset of leakage. Blood oxytocin concentration in ILA cows was low until the start of udder preparation and increased in response to the milking stimulus (reaffirming the hypothesis that milk leakage occurred in the absence of milk ejection). In conclusion, milk losses by leakage are likely due to the large amount of cisternal milk, which creates pressure and causes leakage, in the absence of milk ejection.

Expression by transgenesis of a constitutively active mutant form of the prolactin receptor induces premature abnormal development of the mouse mammary gland and lactation failure.

Prolactin (PRL) initiates signal transduction by inducing homodimerization of PRL receptor (PRL-R). We have previously developed a mutant form of the PRL-R in which a part of the extracellular domain is deleted. This receptor constitutively activates protein gene transcription. We examined the oligomerization of the mutant PRL-R using two differently epitope-tagged receptors in a coimmunoprecipitation assay. It was shown that mutant receptor dimers were formed in a ligand-independent manner, which may explain the constitutive activity on milk protein gene expression. To study the biological activity of this mutant PRL-R on mammary gland development, we generated two lines of transgenic mice expressing the corresponding cDNA specifically in the mammary epithelial cells. For both transgenic lines, the mammary gland of 8-wk-old virgin mice was overdeveloped with numerous dilated ductal and alveolar structures, whereas only a limited duct network was present in wild-type animals at the same age. During pregnancy, the ducts and alveoli of transgenic mice were more developed than those of control animals. At parturition, the transgenic animals failed to lactate and nourish their offspring, and the involution of the mammary gland was strongly delayed. In conclusion, the expression of a constitutively active PRL-R by transgenesis induces a premature and abnormal mammary development and impairs terminal differentiation and milk production at the end of pregnancy.

Lactation defect in mice lacking the helix-loop-helix inhibitor Id2.

Id proteins are thought to be negative regulators of cell differentiation and positive regulators of cell proliferation. Mammary glands of Id2(-/-) female mice reveal severely impaired lobulo-alveolar development during pregnancy. Id2(-/-) mammary epithelia show no precocious maturation, but instead exhibit intrinsic defects in both cell proliferation and cell survival, implying that the role of Id2 in pregnant mammary epithelia is mainly stimulation of cell proliferation and support of cell viability. Expression studies of genes required for mammary gland development suggest Id2 to be a downstream or parallel factor of these genes. A decrease in the DNA binding activity of Stat5 was also observed in Id2(-/-) mammary glands at 7 days post-coitus. Our results indicate an indispensable role of Id2 in pregnant mammary glands.

Investigations on teat canal length in teats with milk flow disturbances.

The objective of this study was to evaluate teat canal length as a test for tissue ruptures in the area of the teat canal in teats with milk flow disturbances (Medl's test). A total of 133 dairy cows affected with milk flow disturbances in one teat were used for this study. The teat canal length of the affected teat was compared with the teat canal length of the contralateral teat of the same cow. Milk flow disturbances were diagnosed by endoscopy. Diagnoses were categorized as tissue ruptures in the area of the teat canal or other causes such as narrowing of the teat canal, or free foreign bodies in the teat cistern. The median teat canal length was 11 mm in teats with milk flow disturbances, and 8 mm in contralateral control teats. When the test criterion was lengthening of the teat canal by > or =2 mm, 79% of the teat canals with tissue ruptures tested positive (true positive), but 47% of teat canals without tissue ruptures also tested positive (false positive). When the test criterion was unchanged teat canal length, 47% of teat canals with tissue ruptures tested positive, and only 7% of teat canals without tissue ruptures tested positive. Thus, it is concluded that Medl's test may be useful in differentiating causes of milk flow disturbances. However, a more accurate diagnosis may be made by teat endoscopy.

New bilateral microcalcifications at mammography in a postlactational woman: case report.

A 33-year-old woman with a strong family history of breast cancer who was referred for mammography 5 weeks after completing lactation was found to have new diffuse bilateral microcalcifications in the breast ducts. Contrast material-enhanced magnetic resonance imaging of the breast showed bilateral patchy areas of abnormal enhancement. Large-core needle biopsy showed diffuse calcifications within expanded benign ducts in a background of lactational change, without evidence of malignancy. To the authors' knowledge, these calcifications have not been previously reported and are possibly related to milk stasis or apoptosis associated with lactation.

[Systematic classification of milk flow obstruction in cattle using endoscopic findings with special consideration of hidden teat injuries]. / Systematische Einteilung der Milchabflussstörungen des Rindes anhand endoskopischer Befunde unter besonderer Berücksichtigung der gedeckten Zitzenverletzungen.

Evaluation of clinical and endoscopic findings in 224 dairy cows, suffering from milk flow hindrance (MFH), led to a systematic categorization. Dairy cows of different age and race, being patients in the Ambulatorische und Geburtshilfliche Veterinärklinik der Justus-Liebig-Universität, Giessen, and the Tierärztliche Klinik Babenhausen, were used as probands. Just a small amount of animals (8.93%) showed causes for MFH that were inborn or non-traumatic, such as inflammations or foreign bodies. In the majority of cases (91.07%) covered teat lesions (CTL) were diagnosed as causes for MFH. The inner orifice of the papillar duct and the papillar duct itself were found to be the by far most frequent locations of traumatic insult, which was diagnosed as avulsion of the mucosa in 86.16% of cases. Minimal invasive endoscopy proved to be a valuable imaging modality to investigate, document and categorize the diverse alterations of the inner teat cistern lining. Basing on clinical and endoscopic findings, MFH is categorized systematically, paying special attention to CTL as its major cause, and illustrated by comparing endoscopic pictures of typical alterations and physiological findings.