J Cutan Pathol 2009: 36: 689–691 Copyright # 2009 John Wiley & Sons A/S

doi: 10.1111/j.1600-0560.2008.01102.x
John Wiley & Sons. Printed in Singapore Journal of
Cutaneous Pathology

Systemic therapy as a first choice

treatment for idiopathic granulomatous
mastitis
Idiopathic granulomatous mastitis clinically and histologically mimics Fausto Maffini1, Federica
an inflammatory carcinoma. A correct approach including ultrasound, Baldini2, Fabio Bassi3, Alberto
clinical and histological analysis can safely identify a patient with this Luini3 and Giuseppe Viale1,4
pathology, orienting to adequate therapy with anti-inflammatory and 1
Division of Pathology and Laboratory
antibiotic drugs and leaving the surgical approach only for case Medicine, 2Division of Melanoma and
unresponsive to medical therapy. Cutaneous Sarcomas, 3Division of Breast
Surgery, European Institute of Oncology,
20141 Milan, Italy, and 4University of Milan
School of Medicine, 20141 Milan, Italy
Fausto Maffini, MD, Divisione di Anatomia
Patologica e Medicina di Laboratorio, Istituto
Europeo di Oncologia, Via G. Ripamonti, 435,
I-20141 Milano, Italy
Tel: 1 39 02 57 48 94 12
Maffini F, Baldini F, Bassi F, Luini A, Viale G. Systemic therapy as Fax: 1 39 02 57 48 94 17
e-mail: fausto.maffini@ieo.it
a first choice treatment for idiopathic granulomatous mastitis.
J Cutan Pathol 2009; 36: 689–691. # 2009 John Wiley & Sons A/S. Accepted for publication June 9, 2008

Idiopathic granulomatous mastitis (IGM), first
described by Kessler and Wolloch in 1972, is a rare
benign inflammatory disease of the breast in young
women.1–3 Clinically and histologically, it is a mim-
icker of acute infection or carcinoma of the breast.3–5
Its etiology is unknown, and autoimmune patho-
genesis has been advocated.1,6 Histologically, the
disease is characterized by the occurrence of numer-
ous granulomatous lesions with multinucleated cells
of the Langhans type and focal central necrosis.
All specific infectious, granulomatous and neo-
plastic diseases must be excluded for a correct
therapeutical approach.
We describe a rare case of IGM of the right breast in
a young Caucasian woman and review the clinical
and pathological features of the disease for its proper
management.
Case report
In November 2005, a 26-year-old Caucasian woman
after two pregnancies was admitted to the hospital for
acute pain in the right breast. Her medical history was
unremarkable. At the first physical examination, a
subcutaneous hard plaque of 7.7 cm in great diameter
in the upper quadrant of the right breast was noted,
without any associated skin lesions or axillary lympha-
denopathy. The prolactin level was not investigated,
but all the routine laboratory tests and specifically
angiotensin-converting enzyme 16 U/l normal range
(n.r. 8.0–52.0 U/l), CA15.3 9.4 kU/l (n.r. , 20 kU/l),
Carcino-embrionary antigen (CEA) 1.4 U/l (n.r. , 3.4
U/l), C-reactive protein 1.0 mg/l (n.r. , 10 mg/l),
Mantoux test negative, Erythrocyte sedimentation
rate (ESR) 2 mm (n.r. 1–10 mm) were within normal
ranges. Despite normal mammograms and chest
X-ray also being normal, the latter performed for
chest pain, a breast carcinoma was suspected and
a needle biopsy was performed, showing a chronic
inflammatory disease with giant cell granulomas.
The ultrasound (US) examination showed an
irregular area with multiple hypoechogenic spots
without features of malignancy.
The patient underwent empirical antibiotic ther-
apy associated with anti-inflammatory treatment,
with a good initial response in terms of pain reduction.

689
Maffini et al.
Six months later, she was re-admitted for subcuta-
neous plaques in the same breast quadrant with mul-
tiple erythematous areas in the overlying skin (Fig. 1).
The clinical aspect was highly suggestive of an
inflammatory breast carcinoma.
Multiple punch biopsies of the skin lesions were
performed, revealing a granulomatous inflammation
characterized by central necrosis, an epithelioid cell
ring with intermingled Langhans-type giant cells,
histiocytes, plasma cells, neutrophils and lympho-
cytes, closely mimicking a tuberculous lesion. Sub-
sequent histological stains for alcohol-acid-resistant
bacteria (Ziehl-Neelsen), protozoa and fungi were
performed with negative results.
A culture from an ulcerated skin lesion was
also performed with evidence of Burkholderia cepacia
(Gram negative), sensitive to Meropenem, piperacil-
lin-tazobactam and trimethoprim-sulfamethoxazole.
A final histopathological diagnosis of IGM was
eventually rendered.
Trimethoprim/sulfamethoxazole BID for 10 days
was administered, followed by a corticosteroid treat-
ment with Prednisone 25 mg/day for 3 weeks, sub-
sequently reduced to 12.5 mg/day for another
3 weeks.
US evaluation after the treatment showed
a remarkable reduction of the lesion with an almost
complete clinical response. Only small residual
cutaneous scars with slight skin pigmentation were
observed, and no pain or other systemic symptoms
were reported. After more than one year of follow up,
the patient remains asymptomatic, without clinical
signs of relapse.
Discussion
IGM occurs in young women and is more frequent in
the Asian population; the average age at diagnosis is
Fig. 1. Clinical skin rash overlying the granulomatous lesions in the
right breast.
690
during the third decade of life. 3,4 It presents as
a palpable lesion in one breast (57%) with associated
pain in 33% of cases. More commonly, the primary
clinical sign is a subcutaneous mass of variable size
(from 1 to many centimeters) that sometimes can
involve all the breast and reach the pectoralis muscle,
being rarely associated with skin ulceration.2 IGM has
an unknown etiology, and it is important to differen-
tiate it from other pathologies, such as carcinoma,
infectious or immunomediated diseases;1 hyperpro-
lactinemia and alpha-1 antitrypsin deficiency. 3–12
As for other inflammatory processes, the axillary
lymph nodes may enlarge and become painful, raising
the clinical impression of an inflammatory carcinoma
with axillary metastasis. A correct diagnosis can only
be reached when additional data from US, histology,
radiological finding and clinical signs and the
histological evaluation are available. The latter is
vital, and for us, it is important to evaluate the lesions
using punch biopsies and to perform the biopsy in the
more affected areas of skin involvement.13
The physical description with lymph node involve-
ments, skin indurations, ulceration and retraction are
typical of breast carcinoma with diffuse skin involve-
ments (inflammatory carcinoma), while as a result of
the IGM showing the same features, the punch biopsy
is a more effective exam for a correct diagnosis.
According to the reported cases, IGM lesions are
generally treated by surgical intervention, antibiotic
therapy being used only to prepare the patient for the
surgical approach treatments. 7
The associated infection with B. cepacia, never
reported in IGM but recently found in chronic
diseases such as a chronic granulomatous disease
and in cystic fibrosis, may contribute to the progression
of the disease due to a decreased phagocytic activity.8
Many authors advocated an autoimmune patho-
genesis of the disease based on the absence of infectious
agents and on the effectiveness of the therapy with
corticosteroids and other immunosuppressive drugs
like methotrexate or azathioprine.9–12,14,15
The very uncommon, and hence unexpected,
appearance of IGM in a young patient from a western
country raises important issues of differential diagno-
sis with inflammatory carcinoma of the breast with
skin involvement and ulceration, nipple inversion,
fistulas and abscesses. 13
Biopsies are mandatory for a correct diagnosis, and
sometimes multiple biopsies are required for lesions
more than 5 cm in diameter mainly in side of skin
involvement. The histological identification of a gran-
ulomatous disease is the first diagnostic clue
(Fig. 2),9,11,16 and it demands a further diagnostic
refinement to exclude other granulomatous diseases,
either infectious (atypical mycobacteriosis, Tubercu
losis TBC, mycosis and protozoosis) or non-infectious
(sarcoidosis, rheumatoid arthritis, erythema

Fig. 2. Granulomatous reaction with giant cells in deep dermis
(hematoxylin and eosin 3200).
nodosum, granuloma annulare and other immuno-
mediated granulomatosis). Despite most previously
reported cases being treated with surgery, this
approach seems to be inappropriate as the first choice
treatment, especially if it leads to total mastectomy.
A therapy with steroid drugs may be considered
a more appropriate treatment for IGM, also in
recurrent or refractory cases after surgery. 9,10 Indeed,
following steroid treatment, 50% of the patients had
a complete resolution of the disease without recur-
rence and another 50% had a stable disease. 17,18
Because the natural history of this disease is self-
limiting, a conservative approach with close surveil-
lance as the first-line treatment is indicated and
a systemic medical therapy can be considered as
advisable.
The surgical approach can be appropriate for
treating recurrences of the disease or the lesions
refractory to the medical interventions.
References
1. Kessler E, Wolloch Y. Granulomatous mastitis: a lesion clini-
cally simulating carcinoma. Am J Clin Pathol 1972; 58: 642.
2. Akcan A, Akyildiz H, Deneme MA, Akgun H, Aritas Y.
Granulomatous lobular mastitis: a complex diagnostic and
therapeutic problem. World J Surg 2006; 30: 1403.
Systemic therapy for IGM
3. Bani-Hani KE, Yaghan RJ, Matalka II, Shatnawi NJ. Idio-
pathic granulomatous mastitis: time to avoid unnecessary
mastectomies. Breast J 2004; 10: 318.
4. Goldberg J, Baute L, Storey L, Park P. Granulomatous mastitis
in pregnancy. Obstet Gynecol 2000; 96: 813.
5. Azlina AF, Ariza Z, Arni T, Hisham AN. Chronic granuloma-
tous mastitis: diagnostic and therapeutic considerations. World
J Surg 2003; 27: 515.
6. Cserni G, Szajki K. Granulomatous lobular mastitis following
drug-induced galactorrhea and blunt trauma. Breast J 1999; 5:
398.
7. Kieffer P, Dukic R, Hueber M, et al. A young woman with
granulomatous mastitis: a corynebacteria may be involved in the
pathogenesis of these disease. Rev Med Interne 2006; 27: 550.
8. McLean-Tooke AP, Aldridge C, Gilmour K, Higgins B,
Hudson M, Spickett GP. An unusual cause of granulomatous
disease. BMC Clin Pathol 2007; 7: 1.
9. Sato N, Yamashita H, Kozaki N, et al. Granulomatous mastitis
diagnosed and followed up by fine-needle aspiration cytology,
and successfully treated by corticosteroid therapy: report of
a case. Surg Today 1996; 26: 730.
10. DeHertogh DA, Rossof AH, Harris AA, Economou SG.
Prednisone management of granulomatous mastitis. N Engl J
Med 1980; 303: 799.
11. Hirata S, Saito T, Kiyanagi K, et al. Granulomatous mastitis
diagnosed by core-needle biopsy and successfully treated
with corticosteroid therapy: a case report. Breast Cancer 2003;
10: 378.
12. Kim J, Tymms KE, Buckingham JM. Methotrexate in
the management of granulomatous mastitis. ANZ J Surg
2003; 73: 247.
13. Heer R, Shrimankar J, Griffith CD. Granulomatous mastitis
can mimic breast cancer on clinical, radiological or cytological
examination: a cautionary tale. Breast 2003; 12: 283.
14. Tuli R, O’Hara BJ, Hines J, Rosemberg AL. Idiopathic
granulomatous mastitis masquerading as carcinoma of the
breast: a case report and review of the literature. Int Semin
Surgical Oncol 2007; 4: 21.
15. Ayeva-Derman M, Perrotin F, Lefrancq T, Roy F, Lansac J,
Body G. Idiopathic granulomatous mastitis. Review of
literature illustrated by 4 cases. J Gynecol Obstet Biol Reprod
1999; 28: 800.
16. Asoglu O, Ozmen V, Karanlik H, et al. Feasibility of surgical
management in patient with granulomatous mastitis. Breast J
2005; 11: 108.
17. Lai EC, Chan WC, Ma TK, Tang AP, Poon CS, Leong HT.
The role of conservative treatment in idiopathic granulomatous
mastitis. Breast J 2005; 11: 454.
18. Erhan Y, Veral A, Kara E, et al. A clinicopathologic study of
a rare clinical entity mimicking breast carcinoma: idiopathic
granulomatous mastitis. Breast 2000; 9: 52.
691