Regional Lymphomatoid Papulosis of the Breast Restricted to an Area of Prior Radiotherapy

Comment

Regional LyP is a rare variant, with only a few reported cases in the literature.^4-18 Scarisbrick et al⁴ originally reported 4 patients with LyP limited to specific regions. Interestingly, one of the patients had mycosis fungoides and the LyP lesions were confined to the same region where the mycosis fungoides lesions were observed.⁴ In a review of LyP in patients from the Netherlands (n=118), lesions limited to a specific region of the body were observed in 13% of cases.⁵ Cases of LyP limited to acral skin also have been reported.^6-8 Heald et al⁹ described 7 patients who had continuing eruptions of papulonodules with histopathologic features of LyP within well-circumscribed areas of the skin. The investigators interpreted this localized variant of LyP as an equivalent of the limited plaque stage of mycosis fungoides. Interestingly, one of the patients with LyP eventually developed plaques of mycosis fungoides in other areas of the skin not involved by LyP.⁹ Sharma et al¹⁰ described an additional example of regional LyP, and Nakahigashi et al¹¹ described a patient with tumor-stage mycosis fungoides who subsequently developed regional LyP involving the right side of the chest. Kim et al¹² described a patient with recurrent episodes of regional LyP exclusively involving the periorbital skin, and Torrelo et al¹³ reported a 12-year-old boy with persistent lesions of LyP involving the skin of the right side of the abdomen. Coelho et al¹⁴ reported a 13-year-old adolescent girl who presented with recurrent papules of LyP exclusively involving the left upper arm. Buder et al¹⁵ reported a case of LyP limited to Becker melanosis. Shang et al¹⁶ described an additional caseof regional LyP that was successfully controlled by interferon alfa-2b and nitrogen mustard solution. Haus et al¹⁷ reported type A LyP confined to the cutaneous area within a red tattoo. Finally, Wang et al¹⁸ reported a case of regional LyP in association with pseudoepitheliomatous hyperplasia

Several dermatoses may appear as specific isomorphic responses to various external stimuli, and it is possible that radiotherapy induces some damage that favors the location of the lesions because the irradiated skin behaves as a locus minoris resistentiae. Pemphigus vulgaris,^19,20 Sweet syndrome,²¹ cutaneous angiosarcoma,^22-32 and cutaneous metastases from malignant melanoma also have been reported to be confined to irradiated skin.³³ However, in our PubMed search of articles indexed for MEDLINE using the terms lymphomatoid papules and regional, none of the previously reported cases of regional LyP had a history of radiotherapy, and in no instance did the lesions develop on a previously irradiated area of the skin.^4-18 The localization of the lesions in our patient could have been the result of the so-called radiation recall phenomenon. Recall dermatitis is defined as a skin reaction in a previously irradiated field, usually subsequent to the administration of cytotoxic drugs or antibiotics.³⁴ It may appear days to years after exposure to ionizing radiation and has mostly been associated with chemotherapy drugs, but recall dermatitis is neither exclusive of chemotherapy medications nor strictly radiotherapy induced. The concept of recall dermatitis has been expanded beyond radiation recall dermatitis to include dermatitis induced by other stimuli, including other drugs, contact irritants, and UV radiation, as well as residual herpes zoster. Nevertheless, in recall dermatitis the triggering drug or agent recalls a prior dermatitis in the involved area, such as sunburn or radiodermatitis. In our patient, there was no history of LyP prior to irradiation of the left breast; therefore, the most plausible interpretation of the peculiar localization of the lesions in our patient seems to be that the eruption resulted as expression of a locus minoris resistentiae.

Distinction between primary cutaneous anaplastic large-cell lymphoma and LyP may be difficult because the histopathologic and immunophenotypic features may overlap. In our case, the presence of several papular lesions and one large nodule are more consistent, from a clinical point of view, with a diagnosis of LyP rather than primary cutaneous anaplastic large-cell lymphoma, which usually presents with a solitary and often large, ulcerated, reddish brown tumor. In our patient, the absence of lymphadenopathy, negative results of the computed tomography of the chest and abdomen, and lack of expression for anaplastic lymphoma kinase in atypical cells of the infiltrate militate against a diagnosis of secondary cutaneous involvement from nodal disease.

The histopathologic differential diagnosis of the current case also included cutaneous CD30⁺ epithelioid angiosarcoma of the breast. Weed and Folpe³⁵ reported the case of an 85-year-old woman who developed a CD30⁺ epithelioid angiosarcoma on the breast after undergoing breast-conserving surgery and adjuvant radiotherapy for treatment of an infiltrating ductal carcinoma of the breast. Histopathology showed a diffuse replacement of the dermis by a highly malignant-appearing epithelioid neoplasm growing in a solid sheet. Neoplastic cells expressed strong CD30 immunoreactivity with absence of immunoexpression for cytokeratins, S-100 protein, and CD45. Additional immunostaining demonstrated that neoplastic cells also expressed strong immunoreactivity for CD31 and the friend leukemia virus integration 1 gene, FLI-1, and focal positivity for von Willebrand factor, supporting a diagnosis of epithelioid angiosarcoma.³⁵ In our patient, CD34 and CD31 were negative, which ruled out the endothelial nature of neoplastic cells.