Introduction. Results. Discussion. Histopathologic and immunohistochemical findings. Results. conclusions,

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3 Carcinoma distinctive carcinoma. form erysipeloides (CE), metastasis. which clinically Itfrom has resembles been termed erysipelas, is an uncommon, but may extend It164 toclassically back, presents proximal as part apapules rapidly evolving even unilateral across chest wall eryma, which Cancer Results Conclusion metastasis.materials Clinical In conclusions, features.represents We examined Methods included retrospectively most metastatic devastating /or breast nodules aspect clinical, carcinoma inflammatory inhistopathologic malignancy 131 ispatients characterized since immunohistochemical in telangiectatic most cases tumor carcino by patien Cutaneous In A Metastatic series this study, metastases we cases examined lesions from skin retrospectively visceral metastases were located malignancies atarm clinical, breast site are carcinoma histopathologic relatively mastectomy rare. observed inmidline The 50 metastatic overall immunohistochemical patients at(80%), mortality Departments incidence elsewhere is estimated feature Derma onsug Clinical features Materials Results Introduction methods Histopathologic immunohistochemical findings In all skin biopsy specimens, histopathologic features adenocarcinoma with varying degrees cell differentiation were observed. The most frequent histopathologic findings were single or multiple nodules located in dermis sub tissue, com posed small to large aggregates tumor cells surrounded by fibrosis. Neoplastic cells were typically arranged in gl-like structures (Fig. 4) or in a linear distribution between collagen bundles in an "indian file" pattern. Telangiectatic carcinoma was characterized by aggregates tumor cells erythrocytes as well as dilated blood vessels in papillary dermis. In erysipeloid carcinoma, histopathologic features were metastatic cells tightly packed within dilated superficial deep lymphatic vessels a slight perivascular infiltrate lymphocytes plasma cells. In carcinoma "en cuirasse", fibrosis with few neoplastic cells sometimes exhibiting a characteristic "indian file" pattern was detected. Histopathologic findings nodular carcinoma or "en cuirasse" carcinoma associated with atrophy hair follicle as a result fibrosis were observed in metastatic lesions scalp. Finally, an epidermotropic pattern characterized by neoplastic cells, single or in small nests, within epidermis dermal aggregates neoplastic cells in a sclerotic stroma was identified in 7/164 patients (4%). Immunohistochemical investigations showed in all patients a strong positivity tumor cells for pan-cytokeratins (PKK1, AE1/AE3, LU5, CK) epilial membrane antigen (EMA) (Fig. 5). In addition, a positive reaction for carcinoembryonic antigen (CEA) was detected in 110/164 cases (67%). Discussion 3/5

4 Cutaneous involvement from breast carcinoma preferentially occurs in skin overlying or proximal to area primary tumor by direct extension or through lymphatic vessels. Nodular carcinoma, inflammatory or erysipeloides carcinoma, telangiectatic "en cuirasse" carcinoma are typical clinical manifestations lymphatic dissemination to skin. Inflammatory carcinoma occurs when neoplastic cells disseminate through lymphatics entire thickness dermis sub tissue. In contrast, telangiectatic carcinoma is characterized by dissemination through superficial lymphatics blood vessels dermis. In nodular carcinoma "en cuirasse" carcinoma, tumor cells disseminate largely along tissue spaces only to a minor degree through lymphatic vessels (6). Although above mentioned clinical manifestations are highly suggestive metastatic breast carcinoma, y may mimic a variety benign malignant disorders as well as occur with cancers or organs. Inflammatory skin metastases may clinically resemble erysipelas but, in contrast to true infection, re is no fever, chills leukocytosis, bacterial cultures are negative (7-11). This clinical pattern may also develop with cancers from or sites such as pancreas, colon rectum, lung, ovary, prostate parotid gl. Telangiectatic lesions have also been reported in carcinoma uterine cervix parotid gl, "en cuirasse" metastatic carcinoma may rarely be seen in kidney, lung gastrointestinal malignancies. Hematogenous spread neoplastic cells is responsible for alopecia neoplastica, which may simulate alopecia areata, sebaceous cyst, scleroderma, morphea-like basal cell carcinoma discoid lupus erymatosus Unusual nonspecific clinical appearances metastatic breast carcinoma have been described. A zosteriform eruption, as observed in one our patients, has been rarely reported most likely results from a perineural lymphatic metastatic dissemination (14,15). The dermatomal distribution vesicular lesions may clinically resemble herpes zoster. However, site lesions, presence malignant cells within vesicles a negative viral PCR or culture allow to establish definite diagnosis metastasis. Metastatic breast carcinoma presenting as a reddish nodule on tip nose has been described defined "clown nose" for its peculiar clinical feature (16). In addition, breast cancer inframammary crease may appear, mainly in women with pendulous breast, as exophytic nodules clinically suggestive a primary squamous or basal cell carcinoma (17). Finally, metastatic breast cancer in eyelid has been reported as a painless swelling eyelid associated with induration or nodule formation. Histologically, it may show characteristics ductal or pleomorphic carcinoma as well as a histioid appearance (18). Immunohistochemical studies may be helpful to identify site primary tumor. In our series previous reports, metastatic breast carcinoma stained positively with antibodies to keratin proteins, as well as with anti-cea anti-ema antibodies (6,19). In addition to estrogen progesterone receptors, gross cystic disease fluid protein-15 (GCDFP-15), a monoclonal glycoprotein expressed in apocrine epilial cells metaplastic apocrine tissue, has been described as a useful diagnostic marker for identifying primary as well 4/5

5 as metastatic breast carcinoma (20-22). Recently, Bayer-Garners Smoller suggested that rogen receptors might serve as additional immunohistochemical markers to increase sensitivity for detecting breast cancer in skin metastasis (23). The prognosis patients with metastasis depends on type biological behavior underlying primary tumor on its response to treatment. Skin metastases from breast carcinoma are usually associated with advanced stages disease as observed in our study, refore, in most cases, y represent a poor prognostic sign. Systemic chemorapy is most commonly used treatment whereas specific protocol depends on histopathologic type primary tumor staging patient. Surgical excision, radiorapy, intralesional chemorapy or immunorapy can be used when solitary lesions develop or in late stages disease in order to improve quality life patient. 5/5