Rosen's Breast Pathology, 4e

927

Unusual Clinical Presentation of Carcinoma

A

B

FIG. 33.37.  Lymphatic tumor emboli in the nipple. A,B: Carcinoma cells in lymphatic channels in the stroma of nipples in patients who did not have clinical manifestations of inflammatory carci- noma. Recurrent carcinoma in such patients is likely to have inflammatory features clinically.

slightly less acute clinical course, but ultimately not a better survival, than women with classical primary IBC. Reports in the 1980s and early 1990s described a substan­ tial improvement in prognosis when compared with earlier data for primary IBC with 5-year survivals ranging from 25% to 48% 273–276 and 10-year survival of 32%. 276 Certain clini­ cal features of the disease (including nodal metastases and chest wall adhesion) at presentation and stage at the time of diagnosis have an important influence on prognosis, with a better 5-year survival observed in those with localized than with regional disease. 274,276 Mastectomy was shown in the past to be ineffective by itself and was rarely performed for IBC, 234 but it is now considered an integral part of the multimodality treatment program. Mas­ tectomy has been relatively effective for obtaining local control of the primary tumor when preceded by combination chemo­ therapy followed by radiation. 250,277–281 Treatment with anthra­ cycline-based neoadjuvant chemotherapy followed by surgery and/or radiotherapy can result in local control in at least 80% of patients and 5-year survival rates greater than 50%. 282 Radiation and chemotherapy often cause a diminution in the clinical manifestations of IBC prior to a mastectomy. The effects of treatment include some or all of the follow­ ing: decrease or elimination of erythema, reduction in breast size, loss of cutaneous edema, and decrease in the size of a palpable tumor if present. Enlarged ALNs may also become smaller. In a few patients, clinical signs disappeared en­ tirely (clinical complete response), but residual carcinoma was found microscopically at mastectomy in virtually all cases. 250,275,278,280,281,283 Clinical complete response has been reported in 12% to 52% of patients, with pathologic com­ plete response in 4% to 33%. 282 Various sequences of treat­ ment have been shown to reliably improve local control and DFS. Amelioration of edema, erythema, breast enlargement, and tumor mass has been associated with a relatively longer

DFS than has been achieved in patients who do not respond to neoadjuvant treatment. 273,278,284 The clinical description of response to treatment does not always correlate well with the pathologic findings in the mastectomy specimen. Considerable residual tumor, often with substantial lymphatic tumor emboli, may persist de­ spite what appears to be a complete clinical response. Alter­ natively, women reported to have partial or minimal clinical response may prove to have little or no microscopically de­ monstrable tumor. In the latter situation, one typically finds substantial alterations in the mammary parenchyma where the tumor has been destroyed (Fig. 33.38). These changes, varying from simple fibrosis to chronic granulomatous in­ flammation, are described in detail in Chapter 41. Similar effects have been observed in ALNs that were pathologically devoid of tumor after treatment although there appeared to be little response clinically. It has been observed that pathologic findings in the mas­ tectomy specimen predict prognosis more accurately than the clinical assessment of response to treatment. 284,285 In one study, “therapeutic response parameters” associated with the most favorable outcome were complete regression after induction therapy within 8 months of diagnosis and com­ plete regression of inflammatory symptoms within 3 months of neoadjuvant therapy. 276 Patients who exhibit a good re­ sponse clinically and pathologically appear to have the best prognosis. The number of involved ALNs may be a particularly important prognostic factor, and for this reason surgi­ cal staging has been advocated. 285 However, pretreatment with chemotherapy may result in downstaging of axillary involvement in patients who have a response that destroys axillary metastases without leaving residual fibrosis in the nodes. A cytokeratin immunostain can be employed to detect microscopic residual carcinoma in ALNs or in the