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Advances in Anatomic Pathology:
doi: 10.1097/PAP.0b013e3181915ff7
Review Articles

Lupus Mastitis: A Clinicopathologic Review and Addition of a Case

Summers, Thomas A. Jr MD*; Lehman, Michael B. MD; Barner, Ross MD*; Royer, Michael C. MD*

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*Department of Anatomic Pathology, Walter Reed Army Medical Center, Washington, DC

Department of Anatomic Pathology, National Naval Medical Center, Bethesda, MD

Sources of Support: None.

Disclosure: The opinions and assertions expressed are solely those of the authors, and are in no way to be construed to represent the opinions and assertions of the United States Government, the United States Department of Defense, or the Departments of the Army or Navy.

Reprints: Thomas A. Summers, Jr, MD, Department of Anatomic Pathology, Building 2, 6900 Georgia Avenue, NW, Washington, DC 20307 (e-mail: thomas.a.summers@verizon.net).

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Abstract

Lupus mastitis (LM) is a rare presentation of lupus erythematosus profundus or lupus panniculitis, an unusual and rare clinical variant of lupus erythematosus itself in which the inflammatory reaction occurs primarily in the deep subcutaneous adipose. Although not required for diagnosis, essentially all cases of LM present with systemic or discoid lupus. The etiology is uncertain. Histologically it is defined by a lymphocytic lobular panniculitis and a characteristic hyaline sclerosis of the adipose tissue. Treatment is primarily medical due to exacerbation of disease by surgical intervention. A high index of suspicion, and familiarity of the histologic findings, is therefore required to make an accurate diagnosis and prevent further unwarranted diagnostic procedures. Herein, we provide a literature-based review of the clinical, radiologic, and pathologic findings of LM and its treatment and prognosis with the addition of a case for the literature.

Lupus panniculitis (LP) or lupus erythematosus profundus is an uncommon entity, first described in 1883 by Kaposi,1 that typically presents with the onset of firm, mobile, often painful, subcutaneous nodules.2 The overlying skin may appear normal or may exhibit atrophy, ulceration, erythema, violaceous color changes, poikiloderma, hyperkeratosis, or typical discoid lesions.3 Irgang4 followed Kaposi's1 description with the first English description of LP in 1940. Lupus mastitis (LM) is a rare presentation of LP involving the deep subcutaneous adipose of the breast. The first documented case of LM was described by Tuffanelli in 1971,5 and in 1995, Holland et al6 published a report of 2 more cases and a review of the 7 previous cases in the English literature at that time.6 To date 20 cases of LM have been reported in the world literature, primarily in the rheumatologic and dermatologic literature, with 1 case reported in the pathology literature.7 All but 1 of the reported cases8 have shown an association with systemic lupus erythematosus (SLE) or discoid lupus erythematosus (DLE). Herein, we provide an additional case and a concise review of all reported cases with an emphasis on anatomic pathology findings and lessons learned.

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DEMOGRAPHICS AND CLINICAL FINDINGS AT PRESENTATION

As only approximately 20 cases of LM have been reported (or mentioned in reports), epidemiologic data are not readily available and therefore the data for LP are often cited as that for LM. LP occurs in 2% to 3% of large series of patients with SLE.9,10 Women are affected twice as often as men and the majority of patients are between 20 and 60 years of age.11 Discoid lesions are strongly associated with these lesions and can be seen in up to 70% of patients with LP.12 Furthermore, as many as 50% of patients with LP may also have a mild form of systemic lupus. LM may precede,13,14 follow,5–7,10,15–19 or occur concurrently with SLE/DLE. Table 1 summarizes the demographic and clinical data of all previously reported or mentioned cases of LM. As expected, LM is predominantly a disease of woman (10:1), but 2 cases occurring in men have been reported.11,22 The average age at presentation with LM is 37.5 years (13 to 70 range) and there is no identifiable racial predilection. As with LP, the majority of cases present in patients with known diagnoses of SLE or DLE, with 2 cases reported as preceding the diagnosis of SLE/DLE13,14 and 2 cases, including the current addition to the literature, reported without an associated diagnosis of SLE/DLE.8 LM is associated with LP presenting at other sites5,6,8,15,19,20 but may also be the sole manifestation of LP. As LM is commonly found in patients with a diagnosis of SLE/DLE, laboratory abnormalities such as an elevated erythrocyte sedimentation rate, positive antinuclear antibodies, extractable nuclear antigens, and double-stranded deoxynucleic acid antibodies are commonly present, but are not necessary for the diagnosis and have not been present in a number of reported cases.8,19 A rare association with antiphospholipid syndrome has also been reported.13 Associated symptoms are variable, but tenderness and pain at the site are frequently reported. The lesion is typically a deep subcutaneous nodule or swelling, usually described as an irregular, hard or firm, well-circumscribed palpable mass,6,8,10,15,18–20,23 that is suspicious for carcinoma in the majority of reported cases.5–7,13,14,16–18,21,22 LM may present as either a mobile6,10 or fixed mass15,23 without overlying skin involvement,7,18 but usually the overlying skin shows induration and erythema.6,8,9,14,16,17,21,22 Other skin changes may include atrophy, ulceration,8,15,16,20,21 violaceous color change or pigmentation,11 poikiloderma,19 hyperkeratosis,22 or typical discoid lupus changes.23

Table 1
Table 1
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ETIOLOGY

The underlying cause of LP or LM is not known and few hypotheses have been provided or validated. SLE is an autoimmune disease in which organs, tissues, and cells undergo damage mediated by tissue-binding autoantibodies and immune complexes. Although LM can occur in patients without SLE/DLE, the process seems to be immune-related also, given the demonstration of immune complexes in LP/LM lesions by direct immunofluorescence12,16 and the dramatic response of lesions to immunosuppressants.6,8,11,14,16 Others have proposed that LP is an extension of the inflammatory process of the DLE in the overlying skin. When DLE is absent, a vasculitis has been proposed as the culprit.21 Although the cause of LM is not well defined, the development or recurrence of nodules at sites of trauma, injections, or biopsy has been well documented5,13,15,16,21 and this finding further supports an immune-related etiology.

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RADIOLOGICAL FINDINGS

Invariably, almost all cases of LM have radiologic studies performed due to the concern for breast carcinoma. Mammography typically shows dense breast tissue with an irregular, heterogeneous, ill-defined mass (Fig. 1).7,12,21,23 Multiple curvilinear and coarse calcifications are often present suggesting fat necrosis,6,8,11,15,17–19,21 but are not inherently present. Ultrasound findings commonly reveal an ill-defined, heterogeneous mass that is usually hyperechoic, extending into the subcutaneous fat, and may show thickening of the skin overlying the lesion (Fig. 2).7,9,10,14,18,23 The only case reported using contrast-enhanced magnetic resonance imagining showed a heterogeneous mass with rim enhancement on T1-weighted images and a peripheral zone of low signal intensity and a central area of high signal intensity on T2-weighted images.23

Figure 1
Figure 1
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Figure 2
Figure 2
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GROSS APPEARANCE AND HISTOLOGY

Gross examination of submitted tissue has not previously been described, however, our specimen was remarkable for a well-circumscribed, stellate, white-tan area of induration that was subjacent to the skin ellipse (Fig. 3), whereas the remainder of the specimen was composed of lobulated, yellow-tan adipose tissue admixed with fibrous tissue. Histologically, LM shows the same features as LP. The overlying epidermis and dermis is usually without significant pathologic change (Fig. 4), specifically basal layer vacuolar alteration. Most of the pertinent changes are confined to the subcutaneous fat and primarily consist of a lobular panniculitis with a prominent lymphocytic infiltrate (Fig. 5). Perilobular, periductal, perineural, and perivascular lymphoplasmacytic infiltrates are also usually present (Fig. 6). Lymphoid follicles may be seen adjacent to the fibrous septa, and germinal centers are occasionally present. A key to the diagnosis, believed to be pathognomonic by some, is the marked hyaline fat necrosis and sclerosis seen (Figs. 7, 8).24,25 Vasculitis, interstitial mucin (Fig. 9), eosinophils, and calcifications are also seen, but are less constant findings.

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Figure 7
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Figure 8
Figure 8
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Figure 9
Figure 9
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PROGNOSIS AND TREATMENT

LM is a chronic disease with exacerbations and remissions. If left untreated over time, LM results in disfiguring atrophy with scarring and retraction, often with ulceration. Surgical intervention is not needed for the treatment of LM and the least invasive procedures for diagnosis and treatment should be taken to prevent aggravation. Unlike LP, which can be treated topically with corticosteroids under occlusion or with intralesional injection, LM requires oral therapy; the first-line agent is hydroxychloroquine, an antimalarial medication, at 200 mg/day. Remission is usually achieved within 3 to 6 months.6,8,11,14,16 For more complicated cases that do not respond to hydroxychloroquine, systemic steroids have been used as a second-line therapy at doses of 1 mg/kg/day.9,17 They have also been used as a primary medication alone with good effect.13,23 Cyclophosphamide has also been reported as being used with varying results.6,9 Cases which are uncontrolled with increasing doses of hydroxychloroquine and oral steroids may result in mastectomy for control of the disease.9,21

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CONCLUSIONS

Multiple lessons were revealed through the diagnosis of our case and review of the other reported cases. First, and possibly most important, is the need for the contributing physician to submit a complete and accurate clinical history to include pertinent past medical history such as SLE/DLE and the suspected clinical diagnosis. Our case was submitted with a clinical history of “suspicious breast mass, rule out carcinoma,” as many other breast cases are. It was not until a review of the patient's chart was performed by the pathologist that it was discovered that the patient had a 15-year history of LP at other sites and that the clinical concern by the dermatologist, rheumatologist, and radiologist seeing this patient was that of LP involving the breast. Although seemingly insignificant this may have potentially caused an inaccurate or nonspecific diagnosis and significant morbidity to the patient. This point was also highlighted by Nigar et al7 whose patient underwent multiple procedures to establish the diagnosis of LM because the pathologist did not know of the patient's clinical history of SLE.

In the workup of essentially all cases of LM, carcinoma is the main exclusionary diagnosis for which biopsies are usually taken. As mentioned though, a correct and accurate diagnosis using the least invasive procedures possible is key to a good clinical outcome given the propensity for activation/worsening of LM by surgical manipulation.9,10,15,16,21 A nonspecific diagnosis due to unfamiliarity with the histologic findings of LM often leads to more invasive surgical procedures that are unwarranted, to rule out malignancies such as lymphoma or carcinoma, and drastically increase the potential for exacerbation of disease. Patients with LM often have poor wound healing after even a small biopsy13,15,16 and 10% of reported cases have gone on to mastectomies to control the disease after biopsy.9,21

Finally, although the clinical presentation of LM is highly variable, the histology is quite diagnostic. Given that LM/LP may be the only manifestation of lupus erythematosus for some patients, familiarity with the histology of LM and a high index of suspicion provided by a complete and accurate clinical history are needed to make an accurate diagnosis. In patients with a history of SLE/DLE presenting with a rapidly enlarging painful breast mass, LM should be suspected. Histologically, the presence of a lobular panniculitis with hyalinized fat necrosis in the breast is highly indicative of, if not pathognomonic for, LM and even in a patient without a diagnosis of SLE/DLE the diagnosis of LM should be made and a clinical evaluation for other associated symptoms, lesions, or laboratory abnormalities of lupus should be sought. However, if the clinical history is absent or hyaline fat necrosis is not identified, the diagnosis of LM becomes substantially more difficult to definitively make and other etiologies of panniculitis, such as erythema nodosa, morphea profundum, connective tissue panniculitis, and secondary panniculitides must be considered.

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ACKNOWLEDGMENTS

The authors thank Glenda Robles, MD, at the National Naval Medical Center, for her assistance with the translation of some reference materials. The authors thank Marlene J. Severson, MD, at Walter Reed Army Medical Center for providing the mammographic and ultrasonographic images. They also thank Leigh Campbell, PA, at Walter Reed Army Medical Center for her gross photos of the lesion.

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REFERENCES

1. Kaposi M. Pathologie und therapie der Hautkrankheiten. 2nd ed. Vienna: Urban & Schwarzenberg; 1883:642.

2. Arnold HL. Lupus erythematosus profundus: commentary and report of four more cases. Arch Dermatol. 1956;73:15–32.

3. Whitaker-Worth DL, Carlone V, Susser WS, et al. Dermatologic diseases of the breast and nipple. J Am Acad Dermatol. 2000;43(5 Pt 1):733–751.

4. Irgang S. Lupus erythematosus profundus: report of an example with clinical resemblance to Darier-Roussy sarcoid. Arch Dermatol. 1940;42:97–108.

5. Tuffanelli DL. Lupus erythematosus panniculitis (profundus): clinical and immunologic studies. Arch Dermatol. 1971;103:231–242.

6. Holland NW, McKnight K, Challa WR, et al. Lupus panniculitis (profundus) involving the breast: report of 2 cases and review of the literature. J Rheumatol. 1995;22:344–346.

7. Nigar E, Contractor K, Singhal H, et al. Lupus mastitis—a cause of recurrent breast lumps. Histopathology. 2007;51:847–849.

8. Pons S, Ortiz-Medina A. Lupus profundo mamario carcinomatoideo (lupus-mastitis). Arch Argent Dermatol. 1978;28:103–112.

9. Castro GR, Appenzeller S, Soledade C, et al. Mastitis refractory to cyclophosphamide in systemic lupus erythematosus. Clin Exp Rheumatol. 2004;22:786.

10. Chen X, Hoda SA, Delellis RA, et al. Lupus mastitis. Breast J. 2005;11:283–284.

11. Winkelmann RK. Panniculitis in connective tissue disease. Arch Dermatol. 1983;119:336–344.

12. Sanchez NP, Peters MS, Winkelmann RK. The histopathology of lupus erythematosus panniculitis. J Am Acad Dermatol. 1981;5:673–678.

13. De Bandt M, Meyer O, Grossin M, et al. Lupus mastitis heralding systemic lupus erythematosus with antiphospholipid syndrome. J Rheumatol. 1993;20:1217–1220.

14. Carducci M, Mussi A, Lisi S, et al. Lupus mastitis: a 2-year history of a single localization of lupus erythematosus mimicking breast carcinoma. J Eur Acad Dermatol Venereol. 2005;19:260–262.

15. Cerveira I, Costa ML, Garrido A, et al. Lupus mastitis. Breast. 2006;15:670–672.

16. Harris RB, Winkelmann RK. Lupus mastitis. Arch Dermatol. 1978;114:410–412.

17. Bachmeyer C, Goubin I, Berseneff H, et al. Coarse calcifications by mammography in lupus mastitis. Arch Dermatol. 2006;142:398–399.

18. Bayar S, Dusunceli E, Ceyhan K, et al. Lupus mastitis is not a surgical disease. Breast J. 2007;13:187–188.

19. Cernea SS, Kihara SM, Sotto MN, et al. Lupus mastitis. J Am Acad Dermatol. 1993;29(2 Pt 2):343–346.

20. Vidal Pich E, Bianchi C, Bianchi O, et al. Lupus eritematoso profundo y calcinosis cutis. Med Cut ILA. 1972;6:259–264.

21. Georgian-Smith D, Lawton TJ, Moe RE, et al. Lupus mastitis: radiologic and pathologic features. Am J Roentgenol. 2002;178:1233–1235.

22. Fernandez-Flores A, Crespo LG, Alonso S, et al. Lupus mastitis in the male breast mimicking inflammatory carcinoma. Breast J. 2006;12:272–273.

23. Sabate JM, Gomez A, Torrubia S, et al. Lupus panniculitis involving the breast. Eur Radiol. 2006;16:53–56.

24. Fountain RB. Lupus erythematosis profundus. Brit J Derm. 1968;80:571–579.

25. Winkelmann RK. Panniculitis and systemic lupus erythematosis. JAMA. 1970;211:472–475.

Cited By:

This article has been cited 2 time(s).

Annals of Diagnostic Pathology
Lupus mastitis: a review
Rosa, M; Mohammadi, A
Annals of Diagnostic Pathology, 17(2): 230-233.
10.1016/j.anndiagpath.2012.09.003
CrossRef
The American Journal of Surgical Pathology
Lupus Mastitis: An Uncommon Complication of Systemic or Discoid Lupus
Kinonen, C; Gattuso, P; Reddy, VB
The American Journal of Surgical Pathology, 34(6): 901-906.
10.1097/PAS.0b013e3181da00fb
PDF (332) | CrossRef
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Keywords:

lupus mastitis; lupus erythematosus profundus; lupus panniculitis; association with systemic lupus; association with discoid lupus; review

© 2009 Lippincott Williams & Wilkins, Inc.

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