Rosen's Breast Pathology, 4e

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Chapter 33

be classified as T4b or T4c.” 221 Patients with IBC tend to be younger than women with locally advanced carcinoma without an inflammatory component, and their tumors are more likely to be ER negative. 226,245–247 A substantial num­ ber of patients with IBC present with enlarged regional lymph nodes. 234 IBC may be mistaken for a non-neoplastic inflammatory condition because of its rapid onset and the main symptom of pain. 220 Diffuse leukemic or lymphoma­ tous involvement of the breast may simulate inflammatory carcinoma. Immunohistochemistry and Molecular Studies The primary tumor of IBC has been negative for ER and PR in up to 83% of cases. 246,248–251 HER2 overexpression was found significantly more often in inflammatory (41%) than in noninflammatory (19%) breast carcinomas, 249 and there was a trend toward more frequent amplified expression of HER2/ neu in cases with negative ER or with positive lymph nodes. In another study, all 22 samples of IBC were immu­ noreactive for HER2. 248 A transplantable xenograft model of human inflammatory carcinoma displayed the same absence of ER and PR and EGFR as the primary tumor used to de­ velop the xenograft. 252 Overexpression of p53 occurs in up to 84% of IBC. 253–255 Charafe-Jauffret et al. 256 reported that IBC was characterized by the following immunophenotype: high E-cadherin expres­ sion, ER negativity, highMIB1 proliferative index, cytoplasmic MUC-1 (mucin glycoprotein) expression, and HER2 overex­ pression. If all five features were present, there was a 90.5% chance that a tumor was inflammatory carcinoma. There was a 75% likelihood of this diagnosis when any four of five mark­ ers were found. The prognosis for patients with non-IBC that expressed four or five of these markers was not significantly different from the prognosis for patients with IBC. 256

Clinical Features IBC is primarily a clinical diagnosis characterized by ery­ thema of the mammary skin (Fig. 33.30). Typically, the skin is thickened, especially at the edge of the erysipeloid area, with peau d’orange changes that are usually more conspic­ uous over dependent portions of the breast. 234–236 The cu­ taneous changes are due to lymphedema initiated by tumor emboli within dermal lymphatic channels. These changes may extend to the skin of the chest wall (Fig. 33.31). In ad­ vanced cases, the breast is diffusely indurated or a mass can be palpated centrally, but the lesion may not be palpable in earlier stages of the disease. 237 Mammography usually dem­ onstrates skin thickening, and within the breast there may be a mass or diffusely increased parenchymal density. 238–241 However, cutaneous edema is not a specific radiologic fea­ ture of inflammatory carcinoma. 236,242 Calcifications may be present in the parenchymal tumor. Skin thickening, mass lesions, axillary lymphadenopathy, and other abnor­ malities may be evident on ultrasound examination of the patient with inflammatory carcinoma. 241 Positron emission tomography with computerized tomography (PET-CT) and MRI have proven to be particularly effective for the diagnosis of IBC. 243,244 Cutaneous erythema is sometimes localized to the re­ gion overlying a palpable tumor. Detection of a mass may precede the appearance of the skin change. Despite ­Haagensen’s original requirement that the lesion involve at least one-third of the mammary skin to qualify as IBC 232 —a definition still used in the latest AJCC-TNM guidelines 221 — it has been noted that the prognosis of patients with less extensive cutaneous changes may be just as grave as that of women with classical inflammatory carcinoma. 245 Accord­ ing to current guidelines, the “rare case that exhibits all the features of inflammatory breast carcinoma, but in which skin changes involve less than one-third of the skin, should

FIG. 33.30.  Primary inflammatory carcinoma. A: Cutaneous erythema predominantly over the dependent part of the breast. B: Most of the swollen breast is involved, and there is desquamation of the skin.