|Year : 2013 | Volume
| Issue : 3 | Page : 523-525
Bilateral adenomyoepithelioma of breast
Jyoti Bajpai1, Sachin B Punatar1, Alok Gupta1, Rajan Badwe2, Sudeep Gupta1
1 Department of Medical Oncology, Tata Memorial Cancer Centre, Mumbai, India
2 Department of Surgical Oncology, Tata Memorial Cancer Centre, Mumbai, India
|Date of Web Publication||8-Oct-2013|
Department of Medical Oncology, Tata Memorial Cancer Centre, Mumbai
Source of Support: None, Conflict of Interest: None
Adenomyoepithelioma is a rare tumor characterized by proliferation of two different cell populations. These tumors have a variable biological behavior. Majority of them are benign but have a tendency to recur locally. Malignant transformation is rare in this disease and distant metastasis is rarer still. We report here an unusual case of bilateral adenomyoepithelioma at an unusual age and showing a remarkable response to an unconventional drug, tyrosine kinase inhibitor "imatinib".
Keywords: Adenomyoepithelioma, breast, imatinib
|How to cite this article:|
Bajpai J, Punatar SB, Gupta A, Badwe R, Gupta S. Bilateral adenomyoepithelioma of breast. J Can Res Ther 2013;9:523-5
| > Introduction|| |
Adenomyoepithelioma of the breast is a rare tumor with around 150 cases reported in the literature.  These tumors are characterized by biphasic proliferation of both epithelial and myoepithelial cells. Majority of the cases are benign but have a tendency to recur locally. Malignant change has been reported in around 40 cases  and distant metastases even more rarely. In malignant cases, the malignancy arises from either the epithelial or myoepithelial component (or in extremely rare cases from both components). To the best of our knowledge, our case is unique in that this is the youngest case reported in the literature and more so as it responded to the drug imatinib in the dramatic manner which is not known so far.
| > Case Report|| |
A mentally challenged 16 year old girl presented with bilateral breast lumps of two months duration. She had no significant medical past history. She had three multinodular lumps, one in right breast and two in left breast. On evaluating, breast ultrasound showed, multiple, well defined, hypo-echoic nodules of variable size scattered all over bilateral breast parenchyma. A few lesions were conglomerated, others were discrete. No calcification was noted within these lumps. The largest on the right measured 3x2 cm [Figure 2] whereas on the left it measured 3.9x1.8 cm [Figure 3]a. Radiologically, these lesions belonged to Bi RAD category 4A; the largest lesion on the right was Bi RAD category 4B. Biopsy from bilateral breast lumps revealed tubular adenomyoepithelioma of sclerosing adenosis type ([Figure 1]). C-kit was focally positive in epithelial component. Patient could not be operated due to reluctance on the part of her family. Subsequently, she was started on tablet imatinib 300mg once daily on experimental basis, in view of her C-kit positivity. The family was thoroughly counseled regarding experimental nature of the treatment, side effect profile of the drug and prolonged duration of treatment. She was initially followed up monthly and later on every 2-3 monthly. In each visit, a thorough clinical examination along with complete blood counts and liver functions testing was carried out. She showed good clinical response to the drug. A breast ultrasound performed two months after commencing imatinib showed no dominant mass in the right breast. On the left side, the dominant mass had regressed to a size of 3.2 × 1.4 cm [Figure 3]b. She was continued on imatinib. She continued to have clinical benefit for more than a year with a good tolerance to the imatinib. After about 16 months from the diagnosis she presented with poor appetite and lethargy and was diagnosed to have hypothyroidism. Subsequently, she developed pneumonia and had to be admitted for the same. At the time of her hospital admission, she had no palpable lump in her right breast. A solitary 2 × 2 cm lump was palpable in her left breast and another 3x2 cm one near the axillary tail. A CT scan of the thorax confirmed these findings. Despite higher antibiotics and other supportive measures she had waxing and waning course and finally succumbed to pneumonia with sepsis. Although blood culture report showed staphylococcal positivity, microbiological reports of the bronchoalveolar lavage fluid (retrieved after the death of the patient) revealed acid fast bacilli positivity (AFB2+). This suggests the patient might have succumbed to tubercular pneumonia.
|Figure 1: (a) Core biopsy showing a biphasic tumor with epithelial element composed of mature bilayered tubules and acini. (H and E:20), (b) Higher power revealing a prominent myoepithelial layer proliferation. (H and E:400)|
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|Figure 2: Baseline sonographic image of the right axillary tail lesion, measuring 3x2 cms; subsequently, after two months of imatinib therapy the same lesion regressed to subcentimetric size|
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|Figure 3: (a) Baseline sonographic image of the left axillary tail lesion, measuring 3.9x1.8 cms, (b) Sonographic image of the same lesion after 2 months of imatinib therapy, measuring 3.3x1.6 cms|
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| > Discussion|| |
Adenomyoepitheliomas of the breast are extremely rare tumors. First described by Hamperl in 1970,  the second case was only reported in 1983.  Since then a number of case reports and small case series have been published. There is paucity of clinical data of this uncommon tumor. Three case series dealing with the clinical aspects of this entity have been published by Tavassoli et al., Rosen et al. and Loose et al.
This tumor is predominantly seen in female patients; only two male cases have been reported till date. , It predominantly affects middle aged and elderly females. Majority of the reported cases are over 40 years of age. The age range is very wide with the youngest reported case so far being 24 years  and the oldest reported patient being 86 years.  The present case was diagnosed at an age of 16 years, the youngest case till date. Majority of the patients present with symptomatic breast mass; a few may be asymptomatic and picked up on imaging. The lesions tend to be centrally located and are unilateral in most of the patients. The vast majority of them occur without any underlying predisposing syndrome; one case of adenomyoepithelioma coincident with multiple gastro-intestinal stromal tumors in a patient with neurofibromatosis type 1 has been described. 
Pathologically, these tumors are characterized by biphasic proliferation of both epithelial and myoepithelial cells. C-kit mutation  and surface CD117 positivity  have been described in these tumors. Biologically, majority of these tumors are benign. Malignant transformation has been described in around 40 cases in the literature. Distant metastases are extremely rare and occur to the lung, brain, liver and the thyroid. 
The management of both benign and malignant tumors is surgical removal. Local recurrence has been described and is more common if the margin of excision is narrow or there is incomplete excision. Local recurrences are managed by re-excision and multiple re-excisions have been described. Radiotherapy has been used in a few cases with local recurrence. The prognosis of benign and locally recurrent disease is good. Chemotherapy has been used in few malignant cases without much success.  The prognosis of metastatic malignant adenomyoepithelioma is poor, thus far with reported survival of a few months. Because of the lack of experience with these tumors, optimal treatment strategies remain to be determined. 
To the best of our knowledge, imatinib (or any other tyrosine kinase inhibitor) has never been tried in these patients. However, in view of C-kit positivity of the tumor cells and dramatic response to this drug in this very case, it might be prudent to use imatinib as an experimental therapy in other patients to further validate our observation.
A number of adverse effects have been reported with the use of imatinib. Most of these are mild and are reversible on discontinuation of the drug. Skin rash (of various types), fluid retention, bone pains, derangement of liver function tests and rarely prolongation of the QTc interval have been described.  Neutropenia and thrombocytopenia are seen in a small proportion of patients treated with this drug. Imatinib induced interstitial lung disease is a very rare complication of imatinib therapy.  Besides, there are also reports suggesting that imatinib may impair host immune defenses by impairing T-cell activation. Hypogammaglobulinemia has also been reported. It has been proposed that these lead to an increased susceptibility to viral infections (like varicella and hepatitis B) and increased risk of reactivation of tuberculosis. , It is important to be watchful for these adverse effects for patients on imatinib therapy.
Our patient with bilateral adenomyoepithelioma of the breast is unique being the youngest patient reported so far and showing a hitherto unreported response to imatinib. The young age of presentation, bilaterality of disease, accompanied mental retardation and hypothyroidism could represent a novel syndromic association. The dramatic response to imatinib therapy warrants further research. The AFB positivity in this case highlights that one must be vigilant about the possibility of reactivation of Koch's (although our patient had no past history of tuberculosis) and also suggests that Koch's in patients on imatinib therapy may have an atypical presentation and a more fulminant course.
| > Conclusions|| |
We would like to conclude that, only with a proper awareness of this entity, the correct diagnosis can be established. Pathologists need to be aware of this rare tumor. Because of the lack of experience with these tumors, optimal treatment strategies remain to be determined. Patients with unresectable, recurrent or metastatic disease may be given a trial of imatinib therapy; however one should be aware of the side effects of the drug, especially because of the long duration of therapy required. The role of this experimental therapy in this disease should be an area of active research.
| > Acknowledgement|| |
We acknowledge the help of Dr. Tanuja Shet, Department of Pathology, Tata Memorial Hospital, Mumbai for providing pathology images.
| > References|| |
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[Figure 1], [Figure 2], [Figure 3]