Rosen's Breast Pathology, 4e

923

Unusual Clinical Presentation of Carcinoma

status. Guth et al. 264 reported that the prognosis of patients with clinically evident noninflammatory cutaneous involve­ ment by carcinoma was significantly less favorable than that of patients with skin involvement that was not clinically apparent. The 5-year distant DFS was 56.9% in the former group and 82.0% in the latter. Secondary Inflammatory Carcinoma The term “secondary IBC” refers to metastatic foci with in­ flammatory features in the skin of patients most of whom did not have primary inflammatory carcinoma. It more of­ ten develops on the chest wall at the site of prior mastectomy than at sites of distant cutaneous metastases. 265 Clinically, the inflammatory form of recurrent carcinoma is character­ ized by discoloration, edema, and peau d’orange appearance of the skin, similar to primary inflammatory carcinoma. Oc­ casionally, secondary inflammatory carcinoma is limited to the treated region in patients who received postoperative radiotherapy, or it may occur only outside of an irradiated field (Fig. 33.32). Palpable tumor infiltrates are commonly found clinically in the skin. 265 Inflammatory changes are not specific for mammary carcinoma, since they have been re­ ported in skin metastases from carcinoma of the pancreas, stomach, lung, and other sites. 266,267 Gross Pathology Patients with primary IBC have an underlying invasive mam­ mary carcinoma. The primary tumor is typically indistinct— clinically, radiologically, and pathologically. If a mastectomy is performed, the size of the tumor may not be recorded be­ cause the gross margins cannot be defined (Fig. 33.33). Fre­ quently, the breast is said to be diffusely involved, or a large tumor is described. 268 As a consequence, accurate data about the size distribution of the primary tumors are unavailable. In one series, localized tumors measured 2 to 12 cm (averaging

FIG. 33.31.  Inflammatory carcinoma. Spread to the chest wall is evident.

In comparisons of samples from primary IBC before and after neoadjuvant chemotherapy, two groups of investiga­ tors found no significant difference in immunohistochemi­ cal HER2 expression. 257,258 Overexpression of HER2 was also maintained in metastatic carcinoma foci. Arens et al. 258 also documented the absence of changes in HER2 expression in pre- and posttreatment samples of the primary tumor by fluorescence in situ hybridization (FISH) analysis. There were no significant differences in the expression of ER and PR and p53 between pre- and posttreatment samples from primary carcinomas. IBC exhibits prominent angiogenesis, as evidenced by high microvessel density (MVD) 259 and a high endothelial proliferation index. 260 It has been reported that a number of angiogenesis-related genes are upregulated in IBC 261 and that some angiogenic factors are overexpressed in these tumors. 262 Angiogenic factors are likely to be targeted as the treatment of IBC evolves. Wedam et al. 263 described the antiangiogenic effect of bevacizumab, a recombinant humanized monoclo­ nal antibody to vascular endothelial growth factor (VEGF), which was given prior to and during anthracycline and taxane neoadjuvant treatment of 21 patients with inflammatory and locally advanced breast carcinoma. After anti-VEGF treat­ ment alone, expression of the phosphorylated tyrosine kinase receptor VEGFR2 in tumor cells was reduced by a median of 66.7%, and apoptosis in the tumor increased by a mean of 128.9%, but there was no change in MVD or in VEGF-A expression. Dynamic contrast-enhanced MRI yielded results indicative of reduced angiogenesis. Antiangiogenic effects of bevacizumab were also observed when the monoclonal anti­ body was administered with combination chemotherapy. Noninflammatory Cutaneous Involvement by Breast Carcinoma The histopathologic finding of tumor emboli in dermal lym­ phatic channels without characteristic clinically evident cu­ taneous manifestations does not qualify as IBC. Staging in this group should be based on tumor size and axillary nodal

FIG. 33.32.  Recurrent inflammatory carcinoma. Inflam- matory carcinoma appears to be restricted to the area of radiation on the chest wall and clavicular region.