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Bilateral breast edema: case report and review of the literature

: Both benign and malignant conditions related to regional or systemic disorders could be included in the diﬀerential diagnosis of bilateral breast edema. Some of them are very often unilateral including stromal inﬁltration and lymphatic obstruction presented in “peau d’ orange” which is the usual presentation of breast cancer. However, the term “idiopathic” could be included in the spectrum of diagnoses. Here, we present a woman of 78 years old who came in our breast unit with bilateral, painless edema of the breasts (appeared one month ago). Clinical examination revealed both breasts swollen with widespread erythema and the appearance of an orange peel/“peau


Introduction
Both benign and malignant conditions could be included in the differential diagnosis of bilateral breast edema although some of them are very often unilateral[ ]. As an example, in "peau d'orange"[ ], stromal infiltration and lymphatic obstruction is almost exclusively a unilateral involvement of both skin and breast parenchyma (which is the usual presentation of breast cancer as a unilateral tumor). Bilateral breast edema can be correlated to rare regional or systemic conditions [ , ] or can be occurred after breast-conserving surgery with radiotherapy or in the postpartum period.
The purpose of this study is to briefly review possible etiologies of bilateral breast edema apropos of one case presented in our breast unit and included in the thesis of the first author.

2a. Clinical history
Here, we present a 78 years old woman who came in our breast unit with bilateral edema of the breast appeared one month ago. Her past medical history was negative including heart/lungs/kidney/liver/endocrine disease without any therapeutic or preventing medicine apart from an antihypertensive agent (prescribed, for the first time, three months ago, and after normalization of blood pressure, it was discontinued without hypertension relapse 2 months ago). Breast cancer personal and family history were negative. No pharmaceutical or other interventions were reported related to the abovementioned condition.
Abstract: Both benign and malignant conditions related to regional or systemic disorders could be included in the differential diagnosis of bilateral breast edema. Some of them are very often unilateral including stromal infiltration and lymphatic obstruction presented in "peau d' orange" which is the usual presentation of breast cancer. However, the term "idiopathic" could be included in the spectrum of diagnoses. Here, we present a woman of 78 years old who came in our breast unit with bilateral, painless edema of the breasts (appeared one month ago). Clinical examination revealed both breasts swollen with widespread erythema and the appearance of an orange peel/"peau d' orange". On palpation, the breasts were not sensitive, and no tumor was palpable. However, clinically palpable lymph nodes were found in both axillas. Her temperature was normal. Breast edema could not be explained from her medical history nor the medications taken. Breast ultrasound, Mammography and Magnetic Resonance Imaging were nonconclusive (BI-RADS 0) and bilateral core biopsy was negative for cancer. Anti-inflammatory plus antibiotic therapy was prescribed for 10 days and at the end of treatment, regional redness and edema were disappeared and reduced respectively. Total recovery was found one month after the initial findings. It can be concluded that bilateral breast edema is correlated to regional or systemic conditions or it is presented as an "idiopathic" disorder of unknown etiology.

2b. Symptoms and duration
The patient complained about discomfort, swollen breasts and breast heaviness but no pain for the last four weeks before her arrival in our unit. Her temperature was normal (36.8 C). No other accompanying symptoms were reported apart from sleep difficulties during the last month which interpreted by the woman as a consequence of her condition.

2c. Clinical examination and initial assessment
Clinical examination revealed both breasts swollen (increased volume of the breasts) with extended redness and the appearance of an orange peel/"peau d' orange" (

2d. Tests
Breast ultrasound (Fig. 2), Mammography (Fig. 3A, Fig. 3B, Fig. 3C) and Magnetic Resonance Imaging ( Fig.   4) were non-conclusive (BI-RADS 0). Considering the rare case of a bilateral malignancy and the peau d' orange appearance, core biopsy was deemed necessary for both breasts, including both actual breast tissue and skin. The day of core biopsy, clinically palpable lymph nodes were significantly shrunken in the left axilla and were not palpable in the right axilla and no further investigation of the axilla region deemed necessary.

2e. Pathology results
Pathology results were negative for cancer and for any specific pathology. The glandular component revealed atrophic glands with fibrosis. Dilated blood vessels and a mild chronic perivascular inflammation (mainly lymphocytes infiltration) were reported for the chorion and skin (Fig. 5A). The immunochemistry staining with AE1/E3, CD34 and podoplanin was negative (Fig. 5B). No malignant cells or precancerous lesions were reported.

Medical therapy and follow-up
The patient was informed that no diagnosis was done, and we proposed a blind antibiotherapy (Amoxicillin-Clavulanate 500 mg orally every 12 hours) plus anti-inflammatory (Ibuprofen 200 mg orally every 6 hours) treatment as a therapeutic test for 7 days. The patient complied with the treatment and no side-effects were reported. After the end of medical therapy, precisely on day 12, regional redness and edema were disappeared and reduced respectively. Total recovery was found one month after the initial findings (Table   1) and no recurrence was reported one and two months later.  10.
An idiopathic case of bilateral breast edema was concluded Figure 1A. Clinical appearance of the right breast (increased volume, intense redness, "peau d' orange").

Discussion
Bilateral breast edema can be correlated to rare regional or systemic conditions [ , ] or can be occurred imaging findings, only the biopsy could exclude or affirm the diagnosis of inflammatory breast cancer. In our case, clinical, imaging and pathologic findings were negative for a formal diagnosis and bilateral breast edema (including the sign of "peau d' orange") was characterized as "idiopathic". The major limitations of our case report presentation is that no cause-effect relationship was established and that it is not definitely known if breast edema resolved solely as a consequence of medical therapy. However, the strength of our approach to this case is the meticulous clinical, imaging and pathologic investigation and the close followup of the patient that give us the confidence to characterize the case as idiopathic. Considering the age of the patient ("Geriatric case") and that this is the first case published with bilateral idiopathic breast edema, thoroughly investigated by the second, the third and the fourth authors, the term "ZerIatric Breast" Disease (ZIBD) was adopted by the writing team of the paper, in parallel with other diseases and/or syndromes of unknown causal relationship. The hypothesis of bilateral breast edema of unknown etiology or "idiopathic" breast edema should be further investigated in a broader spectrum of ages.

Conclusions
Bilateral breast edema can be correlated to some regional or systemic conditions, rarely to bilateral inflammatory breast cancer or it can be presented as a rare temporary disorder of unknown etiology (idiopathic) as in our case. After a negative biopsy, a trial treatment could be proposed along with close follow-up. The term "idiopathic" could be included in the spectrum of diagnoses. contributed to interpretation of data and approved the final version of the paper.
Funding: This research received no external funding.