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20 January 2023: Articles  USA

Carcinoma Erysipeloides: An Underdiagnosed Phenomenon of Cutaneous Metastases of Breast Cancer

Challenging differential diagnosis, Rare disease

Erinie Mekheal1ABCDEF, Brooke Kania1ABCDEF*, Richard A. Hawran1ABCDEF, Poona Kumari1EF, Vinod Kumar2EF, Michael Maroules2EF

DOI: 10.12659/AJCR.937843

Am J Case Rep 2023; 24:e937843

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Abstract

BACKGROUND: Cutaneous metastatic breast cancer is a rare manifestation. Causes include vascular or lymphatic spread or iatrogenic mechanisms following surgery. A sub-type of this disease process, “Carcinoma Erysipeloides,” represents subcutaneous and dermal tissue layer invasion via lymphatic spread. Diagnosis can be challenging, and therefore, obtaining a thorough history and physical, with careful inspection of prior surgical scars is essential for an accurate diagnosis. Lesions present in variable ways, including papules, plaques, ulcerations, nodules, crusting, or fungating masses, with common locations in the chest, scalp, abdomen, and less commonly the arms. When carcinoma erysipeloides is identified, it is imperative to evaluate for distant metastases. Recent literature has identified benefits with trastuzumab deruxtecan therapy instead of trastuzumab emtansine, with decreased progression rates and decreased mortality rates. Metastasis to the skin can indicate advanced disease; however, this metastatic site may be preferable to visceral organs or bones in terms of prognosis.

CASE REPORT: We present a rare manifestation of metastatic breast cancer in 45-year-old Hispanic woman, status post neoadjuvant chemotherapy and radical cystectomy on maintenance trastuzumab and pertuzumab. We discuss the clinical presentation variability, keys to diagnosis, treatment considerations, and outcomes for this unique patient population.

CONCLUSIONS: Carcinoma erysipeloides varies in clinical presentation, especially when patients develop exclusive skin lesions. We identify common etiologies for this progression of disease and discuss combination therapy which has demonstrated a reduction in mortality in this patient population.

Keywords: Breast Neoplasms, Inflammatory Breast Neoplasms, trastuzumab deruxtecan

Background

Cutaneous metastatic disease is rare, encompassing approximately 1% to 10% of metastatic cancers, with breast cancer accounting for 30% of these cases, and the incidence increases with age [1,2]. Metastatic cutaneous lesions include sarcomas, melanomas, hematopoietic cancers, and carcinomas [1]. Cutaneous malignancies typically occur in the setting of widespread metastatic disease, months to years following initial diagnosis [1]. Less commonly, they can present as the first manifestation of malignancy [1]. Ultimately, patients who demonstrate recurrent disease via cutaneous manifestations have been shown to have a worsened prognosis [1]. Here, we present a rare case of a young woman who developed skin lesions appearing as a benign rash, found to be biopsy-proven recurrent inflammatory breast carcinoma, which was subsequently treated with trastuzumab and deruxtecan.

Case Report

A 45-year-old Hispanic woman with a past medical history of stage IIIc left inflammatory breast cancer with ER/PR negativity and HER-2/Neu positivity presented to the Hematology-Oncology clinic for routine follow-up. In terms of her cancer history, she had biopsy-positive ductal adenocarcinoma with ER/PR negativity and HER2 positivity with Ki67 of <10%. The patient previously underwent neoadjuvant chemotherapy with docetaxel, carboplatin, trastuzumab, and pertuzumab (TCHP) followed by a left-modified radical mastectomy, in which her post-mastectomy cancer staging was ypTis (DCIS) N0 (i+) Mx. She underwent 2 weeks of radiation therapy. Her postoperative course was complicated by the development of recurrent seroma without evidence of infection, in addition to chemo-port-related thrombosis with subsequent port removal. Since then, the patient has received maintenance therapy with trastuzumab and pertuzumab.

The patient presented with a rash on the upper aspect of her abdominal wall, localized under her left inframammary fold a few weeks after completion of radiation therapy and 5 months after surgery (Figure 1). At the time, the patient noted painful, burning, mildly pruritic, swollen, non-bleeding, and erythematous rash. She denied subjective fevers, chills, unintentional weight loss, appetite loss, or dizziness. She was referred to Dermatology and was treated with topical steroids, which provided initial relief. Her symptoms later worsened and the rash progressed across her abdomen. Given the steroid-refractory rash, the patient underwent a biopsy of her rash, demonstrating atypical cells that were immunohistochemically positive for CK7, GATA-3, and Her2/neu and negative for ER, findings consistent with the patient’s clinical history of metastatic ductal adenocarcinoma (Figure 2). PET-CT imaging was negative for additional metastatic disease. Given this incredibly rare presentation, the patient consented to chemotherapy treatment with trastuzumab and deruxtecan. She has remained clinically stable with mild fatigue following infusions on this therapy regimen, with initial follow-up PET-CT scan to assess response scheduled for 3 months from initiation of therapy. The patient was additionally referred for potential clinical trials if this therapy is deemed unsuccessful in the future.

Discussion

The etiology of skin metastases from breast cancer may be multifactorial, either via direct spread through vascular or lymphatic distribution, or iatrogenic in the setting of surgical intervention (such as mastectomy or lumpectomy) [2]. The most common manifestation of breast cancer skin metastases occurs with, “Carcinoma Erysipeloides” which presents primarily with inflammatory breast cancer patients, and manifests in the subcutaneous and dermal tissue layers via lymphatic channel spread [2]. Approximately 1 year after a radical mastectomy, our patient presented with cutaneous manifestations of the disease. Given her history of inflammatory breast carcinoma and biopsy-proven dermal lymphatic metastases, our patient’s pathophysiology is consistent with carcinoma erysipeloides.

Cutaneous metastatic breast cancer has a variable presentation and may present as flesh-colored or erythematous, ulcerated or smooth papules, plaques, or nodules with or without crusting, and can develop into substantial fungating masses [1,2]. Metastases develop most commonly on the abdomen, the chest, and the scalp, with less common manifestations on the arms, lower abdomen, back, nail beds, or umbilicus [1,2]. Patients may develop symptoms including but not limited to pruritus, erythema, pain or stinging at the lesion site, hardened skin, or a warm sensation [1,2]. Carcinoma erysipeloides may initially be misdiagnosed as a rash given its presentation with erythematous, elevated, tender lesions that are warm to touch and may have a leading edge [2]. An important manifestation to note is metastatic skin lesion development that can occur either at previous surgical sites or at port sites; therefore, inspection of the surgical scars is essential when examining the patient [1,2]. Given our patient’s history of inflammatory breast cancer and new-onset rash, a skin biopsy was obtained to further investigate the spread of the disease. Her case was unique, as she developed metastatic disease exclusively to the skin, with PET-CT findings negative for additional evidence of metastatic disease.

Presence of cutaneous lesions may be an indicator of distant metastases; therefore, evaluation for distant metastasis may need to be completed [2]. Once distant metastatic disease has been ruled out, local therapy may be considered [2]. Although this tends to be less practical given the nature of cutaneous disease to spread multifocally and given the likely history of prior surgeries such as mastectomy, local therapy may include surgical excision of the cutaneous lesion(s) [2]. Additionally, radiation therapy (RT) may be considered; however, studies have not demonstrated curative outcomes, and this would be more of a palliative approach [2]. In addition, inflammatory breast cancer has not demonstrated adequate responses to localized therapy thus far [2].

Treatment recommendations for patients with HER2-positive metastatic breast cancer include trastuzumab emtansine if patients have progressed following combination therapy with a taxane and anti-HER2 antibody [3]. However, a recent study concluded that in this patient population, patients treated with trastuzumab deruxtecan combination therapy demonstrated lower disease progression and mortality rates when compared to trastuzumab emtansine [3]. Given this information, our patient consented to trastuzumab deruxtecan chemotherapy. For breast cancer patients who develop metastatic disease, the typical treatment is chemotherapy indefinitely; however, given our patient’s unique case, if her skin lesions regress there is a consideration for discontinuing chemotherapy given no further metastatic organ involvement.

The presence of cutaneous metastases from breast malignancy may indicate advanced disease and a less favorable prognosis [4]. While patients with breast malignancies have a better prognosis than those with other cancers, the estimated mean survival rate after a diagnosis of cutaneous metastasis is 50% at 6 months. Therefore, a multidisciplinary evaluation is important for quick initiation of treatment [4]. Cutaneous metastases pose a significant risk of infection, as malignant wounds have difficulty healing. Adequate wound care contributes to an improvement in overall quality of life [2]. Metastasis to soft tissue is associated with a better prognosis than to a visceral organ or bone; therefore, if metastases are confined to the skin, patients can be maintained on a treatment regimen for several years [2].

Conclusions

In summary, cutaneous metastatic breast cancer remains rare and variable in clinical presentation, especially with exclusive metastatic disease to the skin organ. Here, we identified common pathophysiologic mechanisms for the development of this disease process, things to consider when suspecting this disease, as well as management considerations based on current literature and guidelines. Our patient ultimately was found to have isolated skin metastases and consented to treatment with trastuzumab deruxtecan. Given the absence of further metastasis on PET-CT imaging, she may be a candidate for discontinuation of chemotherapy pending resolution of her skin lesions. Ultimately, additional research is warranted for this unique patient population to further improve upon accurate clinical diagnoses and appropriate therapeutic regimens.

References:

1.. Cohen PR, Pleomorphic appearance of breast cancer cutaneous metastases: Cureus, 2021; 13(12); e20301

2.. Moore S, Cutaneous metastatic breast cancer: Clin J Oncol Nurs, 2002; 6(5); 255-60

3.. Cortés J, Kim SB, Chung WP, Trastuzumab deruxtecan versus trastuzumab emtansine for breast cancer: N Engl J Med, 2022; 386(12); 1143-54

4.. Putra HP, Djawad K, Nurdin AR, Cutaneous lesions as the first manifestation of breast cancer: A rare case: Pan Afr Med J, 2020; 37; 383

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American Journal of Case Reports eISSN: 1941-5923
American Journal of Case Reports eISSN: 1941-5923