most locally advanced and inflammatory breast cancer are both palpable and visible, although in some cases, the breast is diffusely infiltrated and lacks a dominant mass. Careful palpation of the skin, breasts, and locoregional lymph nodes (axillary, supraclavicular, and cervical) is the initial step in evaluation. Large tumor size, fixation to the chest wall, fixed or matted axillary nodes (clinical N2 disease), or ipsilateral satellite skin nodules connote LABC. (See "TNM staging classification for breast cancer").
The diagnosis of IBC is a clinical one and is based upon the characteristic clinical presentation, defined as "... diffuse brawny induration of the skin of the breast with an erysipeloid edge, usually without underlying palpable mass" [2] . Patients with de novo IBC (primary disease) typically present with pain and a rapidly progressing tender, firm, enlarged breast. The skin over the breast is warm and thickened, with a "peau d'orange" (skin of an orange) appearance (show picture 1). The skin color can range from a pink flushed discoloration initially to redness or a purplish hue that seems to represent ecchymosis (show picture 2). At presentation, almost all women with primary IBC have lymph node involvement, and approximately one-third have distant metastases [17,18] .
Differential diagnosis — Several conditions may be confused with IBC, leading to potentially preventable delays in diagnosis and treatment. Infectious mastitis and breast abscess, which typically occur in lactating women, are generally associated with fever and leukocytosis. The inflammation that can accompany ductal ectasia is usually localized. Leukemic involvement of the breast may mimic IBC, but the peripheral blood smear is usually diagnostic. (See "Common problems of breastfeeding in the postpartum period").
It may be difficult to differentiate IBC from other LABCs or a breast cancer recurrence involving the skin, causing late inflammation. An inflammatory recurrence of a prior noninflammatory breast cancer has been termed secondary IBC. It usually develops on the chest wall at the site of prior mastectomy, but can rarely occur as a distant cutaneous recurrence.
Mammographic findings — Mammography may disclose an obvious tumor mass, large areas of calcification, or parenchymal distortion. Mammographic findings in patients with IBC may include characteristic skin thickening over the breast, with or without a dominant mass. In one series of 92 patients with IBC, an opacity or malignant type microcalcifications were present in 77 and 49 percent of cases, while skin thickening, nipple eversion, or stromal coarsening were observed in 94, 57, and 85 percent, respectively [19] . (See "Diagnostic evaluation and initial staging work-up of women with suspected breast cancer").
A core needle biopsy usually establishes the diagnosis. A full thickness skin biopsy is often obtained if IBC is suspected, since a hallmark of this disease is dermal lymphatic invasion by tumor cells. (See "Pathology and molecular pathogenesis of inflammatory breast cancer").
Clinical staging evaluation — Once the diagnosis is established, the following staging studies are generally recommended (see "Diagnostic evaluation and initial staging work-up of women with suspected breast cancer") [20] : Complete physical examination, including neurologic examination, to evaluate for potential signs of distant metastatic disease Bilateral mammography Blood tests, including a complete blood count and liver function tests Radionuclide bone scan Chest radiograph or chest CT CT scan of the abdomen and pelvis
An advantage of chest CT over chest x-ray is that it can also identify skin thickening, diffuse infiltration of the breast, and the presence of lymphadenopathy or thoracic metastases [21] .
PET scanning appears to be more sensitive for detection of metastases than other modalities, but its clinical utility is uncertain, particularly since the specificity of PET scanning appears lower than with other imaging modalities. Although breast cancer is a Medicare reimbursable diagnosis for PET scanning, it is unclear whether PET should be incorporated into routine staging maneuvers.