aReza Yaghoobi, MD; bAbdolhasan Talaizade, MD; cKaran Lal, BS; dNastaran Ranjbari, MD; aNasibe Sohrabiaan, MD; eAmir Feily, MD aDepartment of Dermatology, Jundishapur University of Medical Sciences, Ahvaz, Iran; bDeparment of Surgery, Jundishapur University of Medical Sciences, Ahvaz, Iran; cDepartment of Pathology, Jundishapur University of Medical Sciences, Ahvaz, Iran; dNew York Institute of Technology College of Osteopathic Medicine, Old Westbury, New York; eDepartment of Dermatology, Jahrom University of Medical Sciences, Jahrom, Iran
Disclosure: The authors report no relevant conflicts of interest.
Abstract
Cutaneous metastases can have many different clinical presentations. They are seen in patients with advanced malignant disease; however, they can be the initial manifestation of undetected malignancies. Inflammatory breast carcinoma is a rare and aggressive form of breast cancer that has a nonspecific appearance mimicking many benign conditions including mastitis, breast abscesses, and/or dermatitis. The authors report the case of a 40-year-old woman with inflammatory breast carcinoma presenting with violaceous papulovesicular lesions resembling lymphangioma circumscriptum and erythematous patches resembling erysipelas. These lesions represent two different types of cutaneous metastases, both of which were the initial signs of inflammatory breast carcinoma in the patient described herein. Skin biopsy of lesions confirmed invasive breast cancer and further prompted a work up for inflammatory breast carcinoma. This case demonstrates the importance of follow-up for all breast lesions, even those considered to be of benign nature, for they can be presenting signs of metastatic breast cancer. (J Clin Aesthet Dermatol. 2015;8(8):47–51.)
Inflammatory breast cancer (IBC) is an aggressive and infiltrative malignancy that most frequently presents with a myriad of nonspecific symptoms and signs of inflammation. The classic peu d’orange presentation represents edema and erythema of the breast skin. It is a rare presentation of breast malignancy with an incidence of up to six percent in the United States population.[1] The international expert panel on inflammatory breast cancer has advised the following criteria supporting a diagnosis of IBC: rapid onset (less than or equal to three months) of edema, erythema (greater than or equal to one-third of the breast), warmth, presence of a palpable mass or adenopathy, nipple retraction/crusting/flattening, core needle biopsy-proven IBC, previously diagnosed mastitis unresponsive to a seven-day course of antibiotics, overall duration less than six months, and skin punch biopsy revealing intralymphatic tumor emboli.[2] Diagnostic imaging, such as ultrasonography, mammography, and magnetic resonance imaging, are often unsuccessful in detecting breast masses; however, these modalities may aid in localizing areas of concern and may identify metastases since up to 30 percent of incidental cases of IBC have been shown to have distant metastases.[3],[4] In fact, a retrospective review of IBC-confirmed patients concluded that a breast mass was visible on mammography in only 15 percent of patients. Other nonspecific findings, however, such as distortion of trabeculae, were very common.[4] IBC clinically mimics a benign bacterial infection of the breast and/or skin, such as mastitis, cellulitis, or abscess. No evidence of breast masses or lumps are usually detected on physical examination. Diagnosing IBC as infection and treatment with antibiotics represents the leading cause of misdiagnosis and delay of treatment.[5] The authors report a rare case of IBC presenting with two types of cutaneous metastases—lymphangioma circumscriptum-like (carcinoma telangiectaticum) and erysipelas-like lesions (carcinoma erysipeloides).
Case report
A 40-year-old woman was originally referred to a general surgeon for erythema and swelling of her left breast. At that time, a clinical diagnosis of mastitis with abscess formation was made and the patient underwent an incision and drainage procedure. Tissue samples were sent for histopathological examination. The pathology report specimen from the left breast indicated fat necrosis. The patient received systemic antibiotics and nonsteroidal anti-inflammatory drugs for one month. Due to lack of response to treatment, the patient was again referred to general surgery. Routine blood and serum biochemistry tests, chest x-ray, ultrasonography, and mammography were performed. Chest x-ray and laboratory tests were insignificant with the exception of an elevated erythrocyte sedimentation rate (51mm/h). Ultrasonography of the breast revealed nonspecific inflammation of the left breast. Mammography revealed an infiltrative pattern due to carcinomatous or inflammatory changes without masses or microcalcifications. One month later, the patient began to complain of excessive and progressive skin thickening of the breast with the additional appearance of distinct skin lesions for which she was subsequently referred to the outpatient dermatology clinic. Physical examination of the left breast showed congestion and inflammation associated with violaceous papulovesicular lesions that were diffusely all over the surface of the left breast (Figure 1), whereas the right breast had ill-defined, erythematous patches resembling erysipelas infection (Figure 1). Bimanual examination of both breasts elicited tenderness to palpation; however, lumps or masses were not noticed on palpation. Further examination revealed 3 to 4 enlarged palpable lymph nodes in both axillae. Two skin biopsies were performed, one from each breast, on both breasts. Histopathological examination of the left breast specimen showed involvement of the superficial dermal lymphatics by anaplastic cells with central necrosis and presence of solid cords and duct-like structures within the mid-dermis suggestive of cutaneous involvement by a malignant neoplasm in the pattern of comedocarcinoma and invasive ductal carcinoma (Figure 2). Skin biopsy from the right breast revealed lymphatic channels filled with atypical cells with large and hyperchromatic nuclei and duct formation (Figure 3). The diagnosis was reported as metastatic skin tumor of breast origin. With the diagnosis of inflammatory breast carcinoma associated with skin metastases, the patient was referred to the oncology department.
Discussion
IBC is a clinicopathologic entity characterized by a rapidly progressing tender, firm, erythematous and edematous breast. Histopathological examination of punch biopsy specimens from IBC breast skin often reveals lymphovascular emboli. These emboli may also be identified in non-IBC patient specimens, but typically less often.[5] Participation of dermal lymphovascular channels along with appropriate clinical signs favor a diagnosis of IBC; however, these histopathological changes are only evident in up to 75 percent of diagnosed patients, and absence of these features with striking clinical features still favors a diagnosis of IBC.[6]
Breast malignancies account for the most common source of cutaneous metastases among all malignancies in women with an incidence approximating 24 percent.[7] There are many specific presentations of cutaneous metastases of breast cancer including cancer en cuirasse, acral infection-like metastases, carcinoma telangiectaticum, carcinoma erysipeloides, alopecia neoplastica, malignant melanoma-like metastases, and nodular metastases.[8–14]
Carcinoma telangiectaticum presents unilaterally distributed to the side of the affected breast. Multiple different presentations of these metastases have been described including papules, vesicles, purpuric plaques, and even angiosarcomatous lesions.[15],[16] Differential diagnoses to consider include lymphangioma circumscriptum, Stewart-Treves syndrome, herpes zoster, sarcoidosis, and dermatitis herpetiformis. However, a past medical history of breast cancer should warrant thorough inspection including a work up for recurrent metastatic disease. Histopathology of specimens from lesions reveal intravascular nests of tumor cells with erythrocytes in absence of a stroma and dilated blood vessels in the superficial papillary dermis.[7]
Cancer en cuirasse often presents post-mastectomy, as an infiltration of papules and/or nodules, and progresses to form plaques that may or may not be confluent. Lesions begin on the chest with potential for local extension.[11] Often, it is described as being morpheaform and can present with pruritus and tenderness. Cases of sclerodermatomyositis-like, keloid-like, and zosteriform carcinoma en cuirasse have been described.[11],[17],[18] Differential diagnoses to consider include morphea, mycosis fungoides, hypertrophic scar, herpes zoster, psoriasis, and sarcoidosis. Biopsy specimens of lesions typically reveal nests of tumor cells in the dermis separated by dense fibrosis.[7]
Infection-like metastases are rare, but represent major diagnostic dilemmas due to their benign appearances. Acral infection-like metastases are very rare and mimic infectious processes presenting with localized erythema, edema, and tenderness. It is for this reason, antibiotics are usually prescribed and healing is not noted, delaying the diagnosis of stage IV cancer.[19] Similarly, carcinoma erysipeloides, as evidenced in this patient, presents as an erythematous plaque with sharp demarcation and can have surrounding papules or nodules.[20] Tenderness and warmth are often appreciated upon palpation, thus mimicking superficial dermal infection prompting antibiotic distribution. The absence of fever in conjunction with a normal white blood cell count is highly suspicious for carcinoma erysipeloides rather than an infectious process.[21] Patients presenting with cutaneous infection-like processes with a past or current medical history of breast cancer should be evaluated with biopsy of lesions in the event infection is suspected and antibiotic use results in no improvement of lesions. Histological evaluation exhibits tumor cells within superficial and deep dilated lymphatic vessels with a perivascular lymphoplasmacytic infiltrate.[7]
The scalp is a common site of breast metastases. Alopecia neoplastica, however, is a less common type of scalp metastases, and presents with single or multiple areas of scarring alopecia.[22] Differential diagnoses to consider include alopecia areata, androgenetic alopecia, tinea capitis, trichotillomania, discoid lupus erythematosus, lichen planus, syphilis, sarcoidosis, and telogen effluvium. Alopecia presenting in a nondiscrete pattern in patients with a past medical history of cancer should be evaluated with a biopsy. Histological examination reveals nests of tumor cells within the dermis and subcutaneous tissue surrounded by dense fibrosis and loss of pilosebaceous units.[23] Other more common scalp metastases include single or multiple asymptomatic focal nodules that are noticed spontaneously due to rapid growth.[22] It is for this reason many physicians recommend that in addition to serial palpation of lymph nodes, inspection and palpation of the scalp be performed.
Metastases may also mimic primary cutaneous neoplasms. Melanoma-like metastases present as heavily pigmented lesions that may or may not have evidence of peripheral pigmented nodules.[24] Histologically, these lesions are very interesting and pigmentation has been reported to be due to epidermotropism of tumor cells that either destroy melanocytes releasing melanin, or due to uptake of melanin by tumor cells through melanocyte transfer.[25] A case of melanoma-like metastasis has also been described in which pigment was of vascular origin and not due to melanocytic involvement.[26] New pigmented lesion(s) in a patient with a past medical history of any type of malignancy should be treated with suspicion, regardless of a clinical appearance. The origin of metastasis varies based on the clinical presentation. Hematogenous dissemination has been defined in cutaneous metastases, such as alopecia neoplastica.[23]
The origin of the other types of metastases, however, is still uncertain. One study, in an attempt to delineate metastatic pathogenesis, performed immunohistochemical analysis of 28 cutaneous metastatic lesions of varying types. Dilated lymphatic vessels were identified in all 28 cases with D2-40, a specific lymphatic marker. The telangiectatic and erysipeloides types were found more commonly to have intralymphatic tumor emboli, suggesting the importance of lymphatics in these variants.[27] The study also found that more than 40 percent of cases had isolated cutaneous metastases in other locations including the flank, back, pelvis, and even the thigh, thus necessitating a full skin examination in suspected individuals.[27]
A clinicopathologic approach must be performed in order to ascertain the specific metastatic presentation. Pathology is the gold standard for making the ultimate diagnosis. Multiple clinical and histologic subtypes may be present within patients, as evidenced by this patient’s presentation, making it essential to look for unusual cutaneous presentations in recently diagnosed IBC patients. Cutaneous metastases foreshadow a poor prognosis because they often represent widespread disease. Surgical excision and radiation therapy for localized control of metastases may be performed with other alternative regimens being chemotherapy, photodynamic therapy, electrochemotherapy, hormonal therapy, laser ablation, and cytostatic therapy.[28–32] Ultimately, a multidisciplinary team with a surgical oncologist and medical oncologist are required to manage systemic disease, with dermatological procedures only aiming at diagnosis and palliation.
Conclusion
Due to the widespread morphologies of cutaneous metastatic breast disease, it is recommended that nonspecific lesions of uncertain significance in reproductive-aged women and beyond be examined with histopathological examination. A clinical breast exam in addition to mammography should be utilized in conjunction with pathological examination to better formulate a diagnosis and gauge management. Cutaneous metastases from breast cancer may not only be localized to the breast; therefore, a full skin exam in suspected and confirmed breast cancer patients should be performed.
References
1. Hance KW, Anderson WF, Devesa SS, et al. Trends in inflammatory breast carcinoma incidence and survival: the surveillance, epidemiology, and end results program at the National Cancer Institute. J Natl Cancer Inst. 2005;97: 966–975.
2. Dawood S, Merajver SD, Viens P, et al. International expert panel on inflammatory breast cancer: consensus statement for standardized diagnosis and treatment. Ann Oncol. 2011;22:515–523.
3. Anderson WF, Schairer C, Chen BE, et al. Epidemiology of inflammatory breast cancer (IBC). Breast Dis. 2005;22:9–23.
4. Yang WT, Le-Petross HT, Macapinlac H, et al. Inflammatory breast cancer: PET/CT, MRI, mammography, and sonography findings. Breast Cancer Res Treat. 2008;109:417–426.
5. Yamauchi H, Woodward WA, Valero V, et al. Inflammatory breast cancer: what we know and what we need to learn. The Oncologist. 2012;17(7):891-899.
6. Bonnier P, Romain S, Charpin C, et al. Age as a prognostic factor in breast cancer: relationship to pathologic and biologic features. Int J Cancer. 1995;62:138–144.
7. Lookingbill DP, Spangler N, Helm KF. Cutaneous metastases in patients with metastatic carcinoma: a retrospective study of 4,020 patients. J Am Acad Dermatol. 1993:29:228–236.
8. Hazelrigg DE, Rudolph AH. In?ammatory metastatic carcinoma. Carcinoma erysipelatoides. Arch Dermatol. 1977:113(1):69–70.
9. Conner KB, Cohen PR. Cutaneous metastasis of breast carcinoma presenting as alopecia neoplastica. South Med J. 2009:102(4):385–389.
10. Parkes Weber F. Bilateral thoracic zosteroid spreading marginate telangiectasia—probably a variety of “carcinoma erysipelatoides” associated with unilateral mammary carcinoma and better termed “carcinoma telangiectaticum.” Br J Dermatol Syph. 1933:45:418–423.
11. Arapovic SJ, Simi L. Cutaneous metastases—carcinoma en cuirasse. Acta Dermatovenerol Croat. 2002:10(3):167–170.
12. Hodge SJ, Mackel S, Owen LG. Zosteriform in?ammatory metastatic carcinoma. Int J Dermatol. 1979:18(2):142–145.
13. Wyatt AJ, Agero AL, Delgado R, et al. Cutaneous metastatic breast carcinoma with melanocyte colonization: a clinical and dermoscopic mimic of malignant melanoma. Dermatol Surg. 2006:32(7):949–954.
14. Wu CY, Gao HW, Huang WH, Chao CM. Infection-like acral cutaneous metastasis as the presenting sign of an occult breast cancer. Clin Exp Dermatol. 2009:34(7):e409–e410.
15. Schwartz RA. Cutaneous metastatic disease. J Am Acad Dermatol. 1995;33:161-182.
16. Dobson CM, Tagor V, Myint AS, Memon A. Telangiectatic metastatic breast carcinoma in lace and scalp mimicking cutaneous angiosarcoma. J Am Acad Dermatol. 2003:48(4): 635–636.
17. Mullinax K, Cohen JB. Carcinoma en cuirasse presenting as keloid of the chest. Dermatol Surg. 2004;30:226–228.
18. Lakshmi C, Pillai SB, Sharma C, Srinivas CR. Carcinoma en cuirasse of the breast with zosteriform metastasis. Indian J Dermatol Venerol Leprol. 2010:76(2):215.
19. Banuls J, Ramon R, Pico C, et al. Cutaneous acral metastasis from breast adenocarcinoma in a male. Eur J Dermatol. 1997;7:511–513.
20. Prabhu S, Pai SB, Handattu S, et al.Cutaneous metastases from carcinoma breast: the common and the rare. Indian J Dermatol Venerol Leprol. 2009:75(5):499–502.
21. Hazelrigg DE, Rudolph AH. Inflammatory metastatic carcinoma: carcinoma erysipelatoides. Arch Dermatol. 1977;113(1):69–70.
22. Kim JH, Kim MJ, Sim WY, Lew BL. Alopecia neoplastica due to gastric adenocarcinoma metastasis to the scalp, presenting as alopecia: a case report and literature review. Ann Dermatol. 2014;26(5):624–627.
23. Johnson WC. Metastatic carcinoma of the skin. In: Elder D, Elenitas R, Jaworsky C, Johnson B Jr, eds. Lever’s Histopathology of the Skin. 10th ed. Philadelphia: Lippincott; 2009: 1155–1156.
24. Micallef RA, Boffa MJ, DeGaetano J, Muscat V. Melanoma-like pigmented cutaneous metastases from breast carcinoma. Clin Exp Dermatol. 2004;29(2):144–146.
25. Azzopardi JG, Eusebi V. Melanocyte colonization and pigmentation of breast carcinoma. Histopathology. 1977;1: 21–30. 26. Newcomb WD, Camb MB. Unusual cutaneous metastasis in carcinoma of the breast. Lancet. 1924;I:1056–1057.
27. Yun SJ, Park HY, Leen JS, et al. Clinicopathological correlation of cutaneous metastatic breast carcinoma using lymphatic and vascular markers: lymphatics are mainly involved in cutaneous metastasis. Clin Exper Dermatol. 2012(37):744–748.
28. Taube AF. Photodynamic therapy: other uses. Dermatol Clin. 2007:25(1):101–109.
29. Jagsi R, Pierce L. Postmastectomy radiation therapy for patients with locally advanced breast cancer. Semin Radiat Oncol. 2009;19:236–243.
30. Zagar TM, Higgins KA, Miles EF, et al. Durable palliation of breast cancer chest wall recurrence with radiation therapy, hyperthermia, and chemotherapy. Radiother Oncol. 2010;97:535–540.
31. Leonard R, Hardy J, van Tienhoven G, et al. Randomized, double-blind, placebo-controlled, multicenter trial of 6% miltefosine solution, a topical chemotherapy in cutaneous metastases from breast cancer. J Clin Oncol. 2001;21:4150–4159.
32. Benevento R, Santoriello A, Perna G. et al. Electro-chemotherapy of cutaneous metastastes from breast cancer in elderly patients: a preliminary report. BMC Surg. 2012;74 01:S6.