Rapid progression of carcinoma en cuirasse breast dermal metastases on ¹⁸F-fludeoxyglucose positron emission tomography–computed tomography

Abstract

Cancer in the dermis of the breast has a poor prognosis. The breast dermis can become malignantly involved primarily in inflammatory breast cancer, through the direct extension of locally advanced breast cancer, or metastatically from an underlying breast mass or a distant primary malignancy (e.g., gastric adenocarcinoma). Breast dermal metastases have the shortest median survival among them. Breast dermal metastases are classified into eight clinicohistopathologic groups, one of which is carcinoma en cuirasse. We present a case of a 52-year-old female with a history of invasive ductal carcinoma, Stage IIIC (pT2N3a), treated with lumpectomy, axillary node dissection, and chemoradiation therapy that recurred as carcinoma en cuirasse breast dermal metastases. Through ¹⁸F-fludeoxyglucose positron emission tomography–computed tomography (¹⁸F-FDG PET-CT) and clinical images, the case illustrates the rapid progression and devastating consequences of carcinoma en cuirasse breast dermal metastases over a 4-month period despite optimal therapy. Furthermore, the case emphasizes the sensitivity of ¹⁸F-FDG PET-CT to detect pathology in the breast dermis. Finally, the case highlights the crucial role that nuclear medicine physicians play in helping clinical colleagues differentiate between the various breast dermal malignant manifestations and benign mastitis, a common confounder in postradiation patients.

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CASE REPORT

A 52-year-old female with a 4.6 cm left breast invasive ductal carcinoma (no special type) was treated with a lumpectomy and axillary lymph node dissection. Pathologic analysis of surgical specimens revealed wide negative surgical margins on the primary mass, and 19 of 25 lymph nodes were metastatically involved, overall consistent with Stage IIIC (pT2N3a) disease. No left breast dermal involvement was initially present. Subsequently, she received adjuvant chemotherapy with Adriamycin, Cytoxan, and paclitaxel and 66 Gy of radiation to the left breast and axilla.

About 1 year later, she represented with fibrosis of the left breast [Figure 1a, white short arrows], and palpable right axillary adenopathy. While biopsy of the right axillary adenopathy indicated recurrent malignancy, the left breast fibrosis was initially clinically favored to represent radiation mastitis, partially attributable to initial punch biopsy results. However, an ¹⁸F-fludeoxyglucose positron emission tomography–computed tomography (¹⁸F-FDG PET-CT) demonstrated an intense hypermetabolic activity associated with the right axillary adenopathy [Figure 1b, black arrows] and broad areas of moderate hypermetabolic activity throughout the left breast dermis and parenchyma [Figure 1c, white arrows]. This indicated that the changes in the left breast represented a site of aggressive recurrence as opposed to benign inflammation. This was confirmed with a repeat punch biopsy. The skin changes in the left breast were subsequently identified as carcinoma en cuirasse breast dermal metastases. Despite aggressive salvage chemotherapy with paclitaxel and carboplatin, an ¹⁸F-FDG PET-CT scan performed 4 months later revealed the progression of metastatic disease with spread to the right breast, with clinical images showing widespread cutaneous ulcerations and excoriations [Figure 1d-f]. Metastatic spread to the right breast dermis was confirmed by punch biopsy which demonstrated invasion of lymphovascular spaces by tumor emboli [Figure 2, black short arrows] in a background of fibrous connective tissue.

Figure 1.

(a-c) Pre-salvage chemotherapy (d-f) Post-salvage chemotherapy

Figure 2.

Postsalvage chemotherapy biopsy

DISCUSSION

Cancer in the dermis of the breast has a poor prognosis. The breast dermis can become malignantly involved primarily in inflammatory breast cancer, through direct extension of locally advanced breast cancer, or metastatically from an underlying breast mass or a distant primary malignancy (e.g., gastric adenocarcinoma). Table 1 describes the differences between these entities. Dermal metastases have the shortest median survival.[11,12] Dermal metastases from underlying breast cancer occur infrequently, with an estimated incidence between 0.6% and 10%.[13] First described by Velpeau in 1838, carcinoma en cuirasse is a particularly aggressive clinicohistopathologic variant of breast dermal metastases with a contractile fibrous texture resembling the metallic chest plate in antique Spanish cavalry armor.[14] Carcinoma en cuirasse accounts for approximately 3% of dermal metastases from underlying breast cancer.[15] Carcinoma en cuirasse is rarely the presenting feature of underlying breast cancer but rather tends to occur later in the course of the disease development or as a sign of recurrence.[13,15] It is also known as scirrhous carcinoma, pachydermia, or Acarcine eburnee.[16] While others have presented ¹⁸F-FDG PET-CT images of this entity,[16,17] this case report represents the first depiction of the rapid progression and devastating consequences. Furthermore, the case emphasizes the sensitivity of ¹⁸F-FDG PET-CT to detect pathology in the breast dermis. Finally, the case highlights the crucial role that nuclear medicine physicians play in helping clinical colleagues differentiate between various breast dermal malignant manifestations and benign mastitis, a common confounder in postradiation patients. Physicians interpreting ¹⁸F-FDG PET-CT images must routinely scrutinize the breast dermis for thickening or hypermetabolism. Such findings warrant recommending direct physical examination with tissue sampling as indicated.

Table 1.

Differentiating malignant lesions of the breast dermis

Category	Inflammatory breast cancer (IBC)	Non-IBC locally advanced breast cancer	Breast dermal metastases
Clinical presentation	Breast erythema and edema (peau d’orange)[1] Often no palpable mass[1] Involves>1/3 of the breast[1] T4d, at least Stage IIIb[1] Younger age at diagnosis (average: 58 years old) than LABC[2] 20%–40% risk of distant metastases at diagnosis[2]	Definition[1,2,3]  Tumors>5 cm in size (T3) with regional adenopathy (N1) or Tumors of any size with direct extension to the chest wall (T4a) or skin (T4b) or both (T4c) regardless of adenopathy or Presence of regional adenopathy: Clinically fixed or matted axillary lymph nodes (N2) or any infraclavicular, supraclavicular, or internal mammary adenopathy (N3) regardless of tumor stage At least Stage IIIa[1] 10% risk of distant metastases at diagnosis[2]	Eight clinicohistopathologic morphologies[4]  Nodular type  Inflammatory  Telangiectatic  Alopecia neoplastica  Carcinoma of the inframammary crease  Metastatic carcinoma of the eyelid  Paget’s disease  Carcinoma en cuirasse Usually from underlying breast cancer Rarely originates from another organ (e.g. stomach)
Skin finding development relative to the initial disease presentation	<3 months[1,2]	>3 months[1,2]	Usually seen as recurrence of disease[5] Rarely may be initial presentation[5]
Continuity with underlying mass	Continuous	Continuous	Discontinuous
Molecular characteristics	More proliferative subtypes (40% HER2+and 50% triple−)[2] >60% mutated p53 tumor suppressor gene[2] Overexpression of RhoC and loss of WISP3 → Increased tumor invasion and metastases [2] High VEGF → Stimulator of tumor angiogenesis[2] E-cadherin and dysfunctional MUC-1 overexpression → Embolus formation and increased metastases[2]	More favorable subtypes (more ER+and HER2−subtypes)[2] 30% mutated p53 tumor suppressor gene[2]	Activation of pleiotrophin and caveolin-1 → Induces tumor growth, angiogenesis, and potential to invade into adjacent spaces[6,7] Loss on chromosome 1p → Inactivation of tumor suppressor genes[8] Decrease in BigH3 and α-catenin → Less cell differentiation and adhesion[9,10]
Median survival	2.9 years[11]	6.4 years[11]	13.8 months[12]

IBC: Inflammatory breast cancer; LABC: Locally advanced breast cancer; VEGF: Vascular endothelial growth factor; MUC-1: Mucin 1, cell surface associated; WISP3: WNT1 inducible signaling pathway protein 3; HER2+: Human epidermal growth factor receptor 2 positive; WISP3: WNT1 [wingless-related MMTV integration site 1] inducible signaling pathway protein 3; RhoC: Ras homolog gene family, member C

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Conflicts of interest

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