Inflammatory breast carcinoma is a rare form of advanced breast cancer which carries a poor prognosis, even with treatment. Diagnosis is reached on clinical and pathological grounds; however, due to its propensity to mimic other conditions, it may often be delayed or missed by attending physicians. This case series describes four patients seen at our institution with a diagnosis of inflammatory breast cancer; 3 patients had a history of previously treated breast malignancy. In these cases, the emergence of a new breast lesion evaded initial diagnosis due to incomplete initial physical examination, falsely reassuring imaging results, lack of recognition that a cellulitis picture can resemble metastatic carcinoma, and inconclusive initial biopsy sections. These obstacles to achieve diagnosis serve to further worsen the prognosis by delaying the initiation of multimodality treatment which can improve survival. The purpose of our paper is to increase awareness among breast cancer specialists of the importance of undressing the patient for basic clinical examination of the breasts, recognition of the appearances of this type of local recurrence of breast cancer, and not to rely purely on ultrasound and mammography due to delay in diagnosis in some of our local cases. Sometimes deeper sections and repeat biopsies are needed to make the diagnosis.
Inflammatory breast carcinoma, or carcinoma erysipelatoides (CE), is a rare and aggressive form of breast carcinoma with a rapidly progressive course. It has an incidence of 1%–6% of all breast cancer presentations in the United States, a rate which has doubled in the past 20 years [
A 62-year-old woman with a history of silicone breast augmentation presented with a nine-month history of erythema of the right arm and upper chest. A breast review had been undertaken, and an ultrasound was normal. She had previously been admitted twice to another hospital with a provisional diagnosis of cellulitis of her right arm, however, remained unresponsive to antibiotic therapy, prompting referral to dermatology by her local doctor. On examination, the right breast was raised higher than the left, the right nipple was inverted, and indurated erythema extended from the upper R breast to the upper arm and back (Figures
(a) The right breast is raised higher than the left breast and demonstrates nipple inversion. (b) Indurated erythema spreads across the right upper breast and upper arm. (c) Indurated erythema across the right upper back. (d) Extensive lymphatic invasion by infiltrative cords of epithelial cells.
A 75-year-old woman presented with a one-month history of erythema and induration of the left chest wall. Three months previously, she had undergone left mastectomy with adjuvant chemotherapy for locally advanced breast carcinoma and was due to begin radiotherapy. The patient was unresponsive to antibiotic treatment for a provisional diagnosis of cellulitis, prompting referral to dermatology. On examination, there was diffuse erythema and areas of purpura on the left chest wall extending to the left back, with induration over the mastectomy scar (Figures
(a) Indurated left mastectomy scar with diffuse erythema and purpura. (b) The skin changes extend into the left axilla and back. (c) Groups of cells with pleomorphic nuclei and pale eosinophilic cytoplasm infiltrating dermal collagen. (d) Dermal infiltration by carcinoma.
A 72-year-old woman presented with a 1-week history of skin erythema over her right breast and right forearm, with worsening lymphoedema. She had a history of right breast invasive carcinoma five years previously, initially treated with lumpectomy, axillary dissection, and adjuvant chemoradiotherapy. Subsequent recurrence of an axillary mass was treated with palliative chemoradiotherapy, with minor response. On examination, the right breast, with lumpectomy scar, displayed patchy erythema with purpuric borders at the sternum, medial aspect of the upper right arm, and over the right scapula. Scattered within the erythema, there were palpable small nodules. Four skin biopsies showed widespread infiltration of the dermis by metastatic adenocarcinoma (Figures
(a) The right breast displays patchy erythema with purpuric borders. (b) High-grade invasive ductal carcinoma infiltrating dermis, with mitotic figures.
A 53-year-old woman had a history of bilateral hormone-receptor-positive breast carcinoma, treated with double mastectomies, axillary clearances, adjuvant chemoradiotherapy, and hormonal therapy. Four years later, she developed multiple skeletal metastases, liver lesion, and mediastinal lymphadenopathy—at this point, therapy was switched from tamoxifen to anastrozole. She presented with a pathological fracture of the right humerus and several weeks of persisting erythema over the left breast and upper arm which was unchanged despite antibiotics, topical, and systemic corticosteroids. On examination, bilateral mastectomies and a port-a-cath were noted. There was patchy indurated erythema over the left breast and nonspecific blanching rash on the lateral aspect of the left upper arm. Biopsies from both regions showed infiltration of dermal lymphatics by metastatic ductal carcinoma, which was hormone receptor negative (Figure
Focus of dermal lymphatic invasion with a mitotic figure.
The diagnosis of CE is made on clinical and/or pathological grounds. The clinical features, first established by Haagensen in 1971 [
Cutaneous metastases from primary internal organ malignancies are rare (3%–5% of patients with internal malignancies) [
CE is subdivided into a primary form, whereby carcinoma and inflammatory changes occur concurrently in a previously normal breast, and secondary, where inflammatory changes occur later in a breast with previous carcinoma—although both entities have similar survival rates [
Once diagnosed, CE rapidly spreads, both locally and systemically. Trials have shown that between 46% and 100% of women have regional lymph node involvement at diagnosis [
The rapid clinical onset and aggressive nature of CE requires that prompt diagnosis be made and therapy commenced as early as possible to improve survival. However, it often presents as a diagnostic challenge as it may be easily mistaken for other clinical entities. Commonly, these include: mastitis, cellulitis, erysipelas [
Diagnosis is confirmed by histologic sampling; however, this is not always reliable due to the variability of dermal lymphatic invasion, reported to be present in specimens obtained in 75% of patients only [
Here, we present a case series of 5 of our patients, some of whom had delay in diagnosis due to lack of recognition that a cellulites-like appearance may actually be metastatic breast cancer.
Treatment of CE previously consisted of surgery alone; however, this produced poor 5-year survival rates reported at less than 10% [
Evidence suggests that response to induction chemotherapy is the most important prognostic factor in disease-free and overall survival [
The previous cases demonstrate that CE can present insidiously and elude diagnosis both clinically and pathologically. Postsurgery for breast cancer, however, may occur not long afterwards and be confused with postoperative cellulitis/inflammation. It should always be a primary differential diagnosis for unilateral chest wall or arm erythema and induration in a history of malignancy. The lesson for clinicians is to ensure that the patient’s upper body is always fully undressed and properly examined. The threshold for a tissue diagnosis should be low if there is no resolution with initial treatment. Multiple deeper sections of the initial biopsy or repeat skin biopsies should be performed if the pathology does not correlate with clinical findings.
The authors thank the patients for their cooperation with the photographs and reports. This paper was presented at the World Congress of Dermatology in Buenos Aires, Argentina, by Dr. ALC Agero. E. K. A. Millar is a Cancer Institute NSW Clinical Research Fellow.