Red nodule on the breast.

A 63-year-old woman living in the countryside referred to our department with a 2-month history of a red nodule localized on the right breast. Histological examination, immunohistochemical analyses and serologic evaluation conducted with ELISA and Western blot were performed. Clinical diagnosis of borrelial lymphocytoma was not possible solely on the clinical presentation of a classical nodular form without lymphoadenopathy. An absence of a referred prior tick bite and a previous or concomitant erythema migrans at clinical presentation rendered a more challenging diagnosis. The fact that the patient lived in the countryside, the appearance of the breast nodule in September, and serologic, histologic, and immunohistochemical analysis facilitated the diagnosis of borrelial lymphocytoma. We report this case to highlight the importance of an investigation of Lyme borreliosis when a patient living in the countryside presents with a red nodule of the nipple and areola.

Introduction

Cutaneous pseudolymphoma refers to a heterogeneous group of benign, reactive T- or B-cell lymphoproliferative processes of multifactoral origin that clinically and/or histologically simulate lymphomas. The inflammatory infiltrate is band like, nodular, or diffuse and is composed predominantly of lymphocytes with or without other inflammatory cells. Depending on the predominant cell type in the infiltrate, cutaneous pseudolymphomas are divided into T- and B-cell pseudolymphomas.[1]

Case Report

A 63-year-old woman living in the countryside referred to our department with a 2-month history of a red nodule localized on the right breast (nipple and areolar region). The patient did not report either a tick bite or the presence of erythema migrans in previous months. The lesion was a smooth, raised, nonscaling, erythematous nodule, with a diameter of 2 cm; this nodule was movable on the plane below, had a tough-elastic consistence upon palpation, and was asymptomatic [Figure 1]. No lymphoadenopathy was present. The fact that the patient lived in the countryside and the appearance of the breast nodule in September led us to the suspicion of a tick-borne bacterial disease.

Figure 1

A smooth, raised, nonscaling, erythematous nodule on the right nipple and areola

Punch biopsy, histological examination, and immunohistochemical analyses were performed.

Immunohistochemistry was performed with monoclonal antibodies directed toward the markers CD3, CD5, CD10, CD20, CD21, CD79a, Bcl-2, Bcl-6, MIB-1, kappa, and lambda chain, as previously described.[2] Serological tests to evaluate the IgG and IgM antibody response to Borrelia were performed using ELISA and Western blot.

Histological examination revealed a normal appearance of the epidermis and an upper location of the dense dermal infiltrate of lymphocytes (“top-heavy” pattern), characterized by the formation of follicles with germinal centers. In the latter localization, centrocytes, centroblasts, and the prominent presence of tingible-body macrophages (“starry sky” pattern) were evident. Moreover, a mixed reactive infiltrate of histiocytes, eosinophils and numerous polyclonal plasma cells was present in the interfollicular areas [Figure 2].

Figure 2

Histological and immunohistochemical analyses revealed a normal appearance of the epidermis and an upper location of the dense dermal infiltrate

Immunohistochemical analyses documented the predominance of CD20+/CD79a+ B-lymphocytes, but also some CD3+, CD5+ T-lymphocytes were found around B-cell areas and CD21+ follicular dendritic cells. B cells appeared CD10, Bcl-2, Bcl-6 negative with a normal degree of proliferation as detected by MIB-1 marker. CD79a+/CD20- plasma cell expressed both kappa and lambda immunoglobulin light chains, revealing a polyclonal pattern.

Serological evaluation revealed significantly elevated IgG values against Borrelia.

On the basis of clinical, histological, immunohistochemical, and serological findings we diagnosed borrelial lymphocytoma, which was successfully treated with doxycycline 100 mg × 2/daily for 20 days and ceftriaxone 1 g/daily 20 days thereafter.

Discussion

Borrelial lymphocytoma cutis is a late cutaneous manifestation of Lyme borreliosis that in general arises some months after the tick bite. The most frequent onset is reported in August and September.[3] In endemic regions, it is the stereotypical example of cutaneous B-cell pseudolymphomas.[45] The lesions are most frequently located on the earlobe in children and in the areolar region or on the nipple in adults. Other rare locations are the nose, scrotum, upper arm, shoulders, nape of the neck, axilla, and back of the foot.[6] Lyme borreliosis is endemic to various areas of Italy and the main vector is the tick Ixodes ricinus, a species widespread in countryside and mountain regions. Several cases of Lyme borreliosis have been reported to the health authorities in Italy since 1990, when systematic national surveillance started. In our area, borrelial lymphocytoma is uncommon, but not rare and it represents the least common manifestation within the spectrum of Borrelia Burgdorferi-associated skin diseases. Nevertheless, information on the epidemiology of these diseases is still scanty, owing to inadequate notification.[578]

In the present case, clinical diagnosis was not possible solely on the presence of a classical nodular form without lymphoadenopathy. An absence of a prior tick bite and a previous or concomitant erythema migrans at clinical presentation rendered a more challenging diagnosis.

Other pseudolymphomas can clinically simulate Borrelial lymphocytoma [Table 1],[1] but the most important differential diagnosis is with malignant large B-cell lymphoma. The key histologic features that suggest lymphocytoma cutis include the presence of a mixed infiltrate that includes histiocytes, eosinophils and plasma cells, in addition to lymphocytes. In lymphocytoma cutis, the infiltrate tends to be “top-heavy,” whereas most lymphomas are centered in the deep dermis. Moreover, unlike the follicles in follicular lymphomas, all of the follicles in lymphocytoma cutis contain numerous tingible-body macrophages. Malignant B-lymphocytes usually show positivity for CD10, Bcl-6 (outside follicles), Bcl-2 (within follicles) and a monoclonal restriction to either kappa or lambda immunoglobulin light chains, whereas benign infiltrates are often CD10, Bcl-6, Bcl-2 negative and exhibit a polyclonal pattern with expression of both light chains.[59] Finally, immunostaining for proliferating cells (detected by MIB-1 marker) is a helpful clue for the diagnosis, revealing a high or normal proliferation rate of the germinal centers cells in most cases, in contrast to the decreased proliferation observed in follicle center cell lymphoma.[10]

Table 1

Depending on the predominant cell type in the infiltrate, cutaneous pseudolymphomas are divided into T- and B-cell pseudolymphomas

We reported this case due to a typical clinical presentation of borrelial lymphocytoma, but without history of prior tick bite, to highlight the importance of Lyme borreliosis in the differential diagnosis of a patient living in the countryside who presents a red nodule on the nipple and areola.