Cutaneous lymphangitis carcinomatosa of breast cancer: a series of 7 cases

We identified all patients with breast cancer who were referred to our department for a skin eruption that was later diagnosed as a CLC from February 2018 to October 2019. We collected clinical and epidemiologic data, the type of breast cancer, the treatments received, the time interval between the diagnosis of breast cancer and the appearance of cutaneous lesions. Skin biopsies were done in all cases. Once the diagnosis of CLC was confirmed, we performed an extension assessment in all our patients. The followup of the patients continued through the oncology unit.


INTRODUCTION
Cutaneous metastases of breast cancer represent a rare secondary location with a poor prognosis. Cutaneous lymphangitis carcinomatosa (CLC) secondary to breast neoplasia is even rarer. Its clinical presentation may be polymorphous and often confusing [1]. We report a series of 7 cases of CLC of breast cancer, with different clinical presentations.

METHODS
We identified all patients with breast cancer who were referred to our department for a skin eruption that was later diagnosed as a CLC from February 2018 to October 2019.
We collected clinical and epidemiologic data, the type of breast cancer, the treatments received, the time interval between the diagnosis of breast cancer and the appearance of cutaneous lesions. Skin biopsies were done in all cases. Once the diagnosis of CLC was confirmed, we performed an extension assessment in all our patients. The followup of the patients continued through the oncology unit.

RESULTS
A total of 7 patients were diagnosed with CLC. The average age was 54, with extremes ranging from 42 to 68.
Initially, breast cancer was treated by surgery (mastectomy in 5 patients, lumpectomy in 2 patients) chemotherapy and radiotherapy in all patients. Two patients were also treated with hormone therapy.
After a period of 1 to 5 years, patients have developed progressive skin lesions for which they were referred to our dermatology department. These lesions evolved for 5 months on average, were resistant to the different symptomatic treatments previously received (topical corticosteroids, oral and systemic antibiotics, antiviral treatment). The accompanying symptoms were pain, pruritus and sensation of burning, depending on the case The skin eruption was variable (Figs. 1 -4). We encountred different clinical presentations: an erysipelatoid rash in 4 patients, a lymphoedema with erythema and swelling in 3 patients, erythematous maculopapular lesions with ulcerations in 3 patients, papulo-nodular eruption in 2 patients, an induration in 1 patient, an enlarged breast in 1 patient. These lesions were located on the pathological breast region (5 cases), on the upper limb (3 cases), and extended on the contralateral breast (3 cases), thorax and abdomen (2 cases) and scapular region (1 case).
Some patients had a combination of multiple lesions (Table 1).
A skin biopsy was performed in each case. It showed in all patients CLC secondary to breast cancer (Fig. 5). Further examination, including magnetic resonance imaging and computerized tomography scans were performed. They revealed solid metastasis in 5 patients. These metastases were cerebral, pulmonary, hepatic and osseous.
After making the diagnosis of CLC, the patients were referred to an oncology center for management.

DISCUSSION
CLC secondary to breast neoplasia is a rarely described entity [1]. A review of the literature (cases published in Pubmed since 1986 and review of bibliographic references of selected articles) found only 30 cases of CLC [2]. Our series is, to our knowledge, the largest series reporting CLC cases of breast cancer.
The skin represents the 12 th site of metastases for deep cancers. Breast carcinoma is by far the most common primary neoplasm resulting in skin involvement [3].
Cutaneous metastases (CM) are present after breast carcinoma in about 23.9% of patients, often involving the chest and abdomen and manifesting on average 5 years after surgical removal of the first malignancy [4]. Typical CM are due to a dense infiltrate of neoplastic cells in the dermis or the hypodermis and are described as unique or multiple dome-shaped, reddish, painful nodules or masses with a moderate to firm consistency, this aspect accounting for 70-80% of cases [5].
Intravascular metastases of breast carcinomas are rare and may spread through dermal blood vessels of dermal lymphatic vessels [6]. Cutaneous lymphangitis carcinomatosa is a rare presentation of skin metastases. It accounts for approximately 5% of all cutaneous metastases. It is characterized by an occlusion of dermic lymphatic vessels by neoplastic cells [4,5]. Various terms have been used in the literature such as lymphangitis carcinomatosa, erysipelas carcinomatosa and metastasis cutis [7].
Clinically, the eruption is polymorphous, able to mimic different dermatoses; thus delaying the diagnosis and proper management of the lesions. It usually presents as an erythematous, tender area closely resembling an acute infectious process, i.e., erysipelas or cellulitis.  However, CLC is not associated with fever, chills, and leukocytosis. Furthermore, CLC shows no response to antibiotic therapies [4,5]. Three of our patients were treated with antibiotics for suspecting erysipelas before correcting the diagnosis with skin biopsy. CLC may also occur as nonspecific eczematiform lesions, angiomatous or sclerodermiform lesions, or in the form of localized lymphedema [2,7,8]. When the diagnosis of lymphoedema is made in patients previously treated for malignancy, the physician must consider whether recurrence is the cause or lymphedema is a complication of the initial cancer treatment. Secondary lymphoedema due to malignant infiltration should be considered particularly when lymphedema develops quickly, is constantly present, dilated veins are visible and patients are complaining of intolerable, intense pain [7].
In the series of 4 cases of Hariz et al, they reported several aspects (papulo nodular and erosive rash, erysipelas, radiation-induced lichen, eczema) [1]. Sometimes, different clinical aspects may exist in the same patient; as was the case for our third patient who presented with both lymphoedema and swelling of the upper limb and induration of the scapular region. Prat and al have also noted in the same patient lymphedema of the root of the limb, with eczematiform, erysipelatoid and angiomatous lesions elsewhere [2].
Our series of 7 patients is a good illustration of the clinical diversity of CLC. The clinical presentations were different from one patient to another. We noted several types of lesions that was diagnosed as CLC, namely an indurated papulo-nodular eruption with ulcerated and crustal lesions, lymphedema with erythema and swelling, erysepelatoid rash and indurated plaque.
CLC has been reported in the literature in association with several malignancies, including lung, breast, ovarian, pancreatic and rectal cancers [2,4,6].
Similar to the other reports in the literature, four of our patients died shortly after the appearance of the CLC. This indicate that lymphogenic spread in the skin might be a sign of lymphogenic metastases elsewhere and possibly also a marker of rapid tumour progression.

CONCLUSION
This report illustrates the clinical polymorphism and the diagnostic difficulty of CLC.
In a patient with a history of cancer, we stress that every cutaneous lesion should alert the clinician to the possibility of a cutaneous metastasis revealing a cancer recurrence. An early histological examination should be performed looking for that entity that may be under diagnosed.

Statement of Human and Animal Rights
All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008.

Statement of Informed Consent
Informed consent was obtained from all patients for being included in the study.